Cancer chemo(toxico)therapy revisited and alternative ways of healing.A thesis presented to the Anglo-American Institute of Drugless Therapy and leading to the Degree of Doctor of Naturopathy (N.D.).
© 1990 by Dr. Henri Rosenberg.
Introduction 2
Chapter I : Chemo(toxico)therapy 3
Chapter II : Amygdalin - Vitamin B 99
Chapter III : The Synthetic Physiatrons 128
Chapter IV : Trypanosoma Therapy 140
Chapter V : Selenium Therapy 146
Chapter VI : The beer's yeast cure 156
Chapter VII : Tumor related indicators 164
Chapter VIII : The Thymus Therapy 188
Chapter IX : The H-11 Therapy 194
Chapter X : Antineoplaston 202
Chapter XI : Gelum Oral RD® 205
Chapter XII : Neoblastine® 212
Chapter XIII : The WIEDERMANN cure 219
Chapter XIV : Beetroot (juice) as cancer therapy 225
Chapter XV : Integral Fasting Therapy 229
Chapter XVI : The Iron Cancer Cure 235
This work, which is presented for the Degree of Doctor of Naturopathy (N.D.)., is the result of fifteen years of self-taught investigations into the field of oncology (the study of cancer).
Part of the investigations are included in this work and, more specifically, a critical analysis of chemotherapy followed by typical examples of substitution therapies that are less harmful and more efficient.
The thorough chapter about chemotherapy gives an exhaustive enumeration of the existing chemical agents (including their brand names worldwide) and brings, probably for the first time, the very harmful side effects (including the cancer-producing) to the attention of the general public. The author's method is based on the indication of the sheer volume of published medical work that supports his thesis. He searched the official medical literature worldwide for the years 1980, 1985 and 1990, thus proving the side effects of chemo-therapeutic drugs in visu by giving the bibiographic reference of the articles. It was evident from them that the titles of most articles were eloquent about these side effects and strikingly different from the reassuring advice given by doctors to the wide audience.
A selection of the so-called soft therapeutic treatments (including the less classical diagnostical means) that is being offered to the reader after this chapter, is meant to show that the criticism on chemotherapeutics is a constructive one. Moreover, each therapy has with it the relevant addresses to give this work a practical side as well.
The author has a Dutch version of the almost complete work in manuscript, including an encyclopædic reproduction of all existing so-called alternative curative and diagnostic methods for cancer.
Antwerp, 20 July 1990.
Dr. Henri ROSENBERG.
Chemo(toxico)therapy.
0.- Introduction.
The purpose of this chapter is manifold. Its principal intention is to provide both patient and unspecialized general practitioner with insight into the classic therapeutic arsenal, the action of therapeutic agents and, more particularly, the many side effects which they produce. This will enable the emancipated patient to decide consciously and with full knowledge of the facts, pro or against a specific therapy.
Indeed, 'specialists' tend to assume that the cancer patient is not emancipated; the patient must not be too well or too precisely informed, and he must actually 'undergo' the treatment willingly as this represents his only and best chance.
For this purpose, both statistics about prognoses, and side effects of the therapeutic agents used, are obscured.
I. Statistics.
Success statistics are being manipulated and fabricated in such an expert and subtle way that they give evidence of some manifest and significant progress in the fight against cancer. In medical circles, this systematic and large-scale deceit is excused by the concern 'not to cause panic' in cancer patients who do not have any serious alternative anyhow than walk the classic therapeutic way. It goes without saying that not only are all alternative ways of treatment en bloc rejected for being useless and even dangerous, but furthermore, the hypothesis that a patient would prefer n o t to be treated and, consequently, live the rest of his life in a qualitative more positive way, is considered to be non-existant. This is even more criminal because the fact that chemo(toxico)therapy would have any effect on cancer patients' life expectations, is far from being proven. On the contrary, comparative studies with non-treated patients have revealed that chemo(toxico) therapy does not produce any life-prolonging effects (1). Untreated patients appear to live (survive) at least as long as treated patients (2).
1. A first manipulation of cure statistics consists in the (theoretic) distinction which is made between early diagnosed and late discovered cancer. The first kind would be easy to treat and even curable, whereas only those cancers which are discovered (too) late would be fatal.
The patient-directed information provided by the different official national cancer institutes thus represent the various chances of recovery (= 5 years of survival), according to the fact whether cancer was discovered early or (too) late. For cancerinoma of the lung, early discovery represents 75% chance of recovery, while later discovery only gives 20% chance. For carcinoma of the gullet, recovery (or better, remission) is possible in 50% of early diagnosed cases, but only in 2% (say two percent !) of late location. Stomach cancers are curable in 90% of cases with early diagnosis, but only in 10% if the disease is detected (too) late. Biliary duct cancer is curable in 25% with early diagnosis and in barely 2% with late diagnosis. Cancer of the intestine offer 80% chance of recovery with early discovery but only 30% if the diagnosis is carried out late. Cancers of female sexual organs offer 75 in 100 chances of being cured of the diagnosis takes place in time. With late diagnosis there are hardly 5 chances in 100 to reach the five years' limit. Breast cancers offer 85% and 25% respectively, kidney cancers 75% and 20%, prostate cancers 80% and 2 to 3% (!) according to early or late diagnosis. For bladder cancers, the chance of survival is 90% in the early stage and 15% in the late stage. Cancers of the osseous system may be remedied in 85% of cases when they were located early; otherwise, there is only a chance of 2% ! Blood cancers and cancers of the hematopoietic system make a chance of 50% of remission with early detection and only 5% when the cancer is discovered late (3).
A suggested conclusion from the above is that cancer can indeed be remedied in a large percentage of cases ... if only it is detected in time. Figures are then quite hopeful : lung cancer 75% chances of survival, stomach cancer 90%, breast cancer 85%, bladder cancers 90%, etc. If, on the other hand, cancer is discovered in a late stage - but who would ever count himself among this category -, figures are alarming : only very low percentages of survival chances.
The trick - or swindle - however consists in that the theoretic early-stage model upon which the entire favourable prognosis statistics are built, is unapproachable in practice. The hopeful early stage, which is referred to in the statistics, is situated at a level when the tumour hardly counts some 4000 cells and has reached a diameter of 0.06 cm. (i.e. after the 13th cell division). At this level, the first micrometastases are already developing, which will escape all forms of later classic therapy. This (real) early stage is purely theoretical because at this moment it is not (yet) possible to be located by means of current modern diagnostic methods. Only from the 21st cell division onwards, when the tumour count two million cells and has acquired a diameter of 1 cm., diagnosis becomes feasible. However, even in the terminology used by the statistics, this is already considered to be a late stage and more alarming percentages of survival will occur. If one is lucky and has a diagnostic examination precisely at the moment when the tumour reaches the 21st cell division - a rarely occurring case - even then, the early stage indicated by statistics has been long exceeded and the category of very low percentages of survival has already been reached; 20% for carcinoma of the lung, 10% for carcinoma of the stomach, 2% for gullet cancer, etc.
These most alarmingly low figures apply in the majority of cases - the so-called early diagnosis is hardly over obtained - and represent, moreover, the real remission chances for the different forms of cancer. In a recent report, the World Health Organization (W.H.O.) (4) has confirmed that hardly any progress in the fight against cancer has been made over the past 25 years. Death following certain widely spread forms of cancer has even increased in a terrifying way.
Over the period 1960-1985 cancer mortality was compared in 28 industrial countries (5). It appeared that death due to cancer has increased in general by 58% for men, and by 40% for women. Today, 40% more men and 200% more women die from cancer of the lung than twenty-five years ago. The chance to die from breast cancer between the ages of 45 and 64 is nowadays 37% higher than in 1960 (6), and consequently, the number of cancer cases also increased in that proportion. If it had not been for this correction, mortality figures in 1985 would have been even higher. Only death as a consequence of stomach cancers has declined by 12% in 25 years. However, the W.H.O.-report does not ascribe this declined mortality with regard to stomach cancers to any therapeutic progress, but rather to improved living and eating patterns :
"In addition it would appear that such factors as non-specific life-style changes have been the major cause of decline in stomach cancer" (7).
2. A second manipulation of statistics is the introduction of an unscientific element in the statistic juggling of medicracy, namely the beginning of the five years' remission period. It is obvious that this period will be longer or shorter according to the fact whether the patient goes to see the doctor from the first suspicious moment, or only after he has experienced certain discomforts. In the first case - the hypochondric patient - the remission period will start off much sooner than in the second case. Statistically, the first patient will therefore 'survive' longer than the second without the chemo(toxico)therapic (or other) treatment having anything to do with it. As far as statistics are concerned, however, it is the treatment which has facilitated the longer survival. This evidence which has incorporated in the remission statistics may be compared with the equally evident 'ascertainment' : the younger the person, the better his/her chance of a longer life. The latter evidence only differs from the former in that it was not elevated to a 'medical success'.
This supplementary deceit of figures helps, furthermore, to keep up the myth 'the earlier discovered, the better the chances of recovery'. Indeed, the first patient in the abovecited example was lucky to have an 'early' diagnosis and will therefore (?) survive longer. For the second patient, the diagnosis was set 'late' and therefore (?) he will not live as long. It goes without saying that the therapy has nothing to de with it and that the longer survival is only owing to the fact that the counting off was started sooner. Nevertheless, such cases are put on by the medical establishment in order to fortify therapy successes.
3. A third purposive and straight falsification of recovery statistics consists in the assumption that the 'remission' limit of five years is only reached thanks to chemo(toxico)therapic treatment. This results, in fact, in the postulation that untreated patients do not have any chance of reaching the 5 years' survival. This hypothesis is even more malicious because - as we mentioned before - investigation has revealed that untreated patient lived (survived) (at least) as long as chemo(toxico) therapically treated patient.
The real figure of recoveries can only be obtained by making the difference between the five years' chance of survival of all patients after treatment, and the five years' chance of survival of the same patient if they had been left untreated. Thus the effectiveness of treatment could be measured and quantified. In medical circles, however, natural survival with cancer is confused and put on a par with the effectiveness of a medical treatment. It is not without any cynism that we remind of the fact that the medical establishment accepts and proclaims that cancer patients who are treated in the classic medical way 'survive', and owe this exclusively to the therapy they followed. When, on the other hand, differently or non-treated patients also 'survive' - and in much better circumstances - they are said to have experienced a 'spontaneous remission' ...
4. However, the medical lobby tends to use many more sophisms in order to prove their successes. Under the cover of 'preferring the certain to the uncertain', borderline or dubious cases have lately been diagnosed and treated more and more like cancers. In itself a noble motivation, of only the applied treatment were not as mutilating and its efficiency not as doubtful. So, for example, terms have been introduced for quasi-cancer diseases such as dysplasia (deformation), carcinoma in situ (cancer which has not yet broken enough the tissue structure), precarcinoma and micro-invasive cancers (8).
This enriched medical vocabulary describing quasi- and pseudo-cancers and, the inevitably ensuing confusion have already produced a terrifying number of unnecessary mutilating operations (especially in the gynaelogical sector and on either side of the female navel) (9) and even harmful chemo(toxico)therapeutic operations (10).
It goes without saying that if non-cancers, pseudo- and quasi-cancers are regarded as cancers 'by way of precaution', the chances of recovery increase with the number of thus diagnosed pseudo-cancers.
5. Another fatal consequence of this medicratic deceit may be illustrated by the following example. When, for example, an experienced physician succeeds in discovering by means of palpation, a mass with a diameter of hardly 1 cm. in the prostate gland which, after hystopathological investigation appears to be a cancer, and if it is removed by surgery, the patient will probably reach the five years' limit and be declared free of cancer, thus adding another case to the list of medical successes. The danger that lurks in this diagnosis is that the micrometastization had already taken place before the operation (11) (during the operation, more malignant cells may have arrived into the bloodstreams (12)) and that a new precancerous phase has been developed which most probably after five, but certainly within ten or fifteen years, will produce a new tumour, while classic therapy will be incapable of avoiding this. For indeed, the therapeutic arsenal of academic medicine is only armed against tumours and completely ignores the initial phase, the cancer d i s e a s e which preceeds the tumour phase. Biological alternative therapies on the other hand do have an eye for the cancerous disease and, for the precancerous lead-up which takes many years, and claim to be capable of eliminating the disease in the pretumourous stage. However, medicracy usually deprives the cancer patient of this possibility. In this case, the alternative methods do not even enter the (private hunting-) field of academic medicine, because, as we have said before, classic therapy does not even claim to combat the precancerous lead-up phase. Alternative approaches therefore are the only and, consequently, the best chances of preventing the 'cured' cancer from being succeeded by a new one. Nonetheless, this alternative is being denied to the 'cured' patient who takes his declaration of recovery much too literally and irrevocably.
Conclusion.
As a conclusion we may openly accuse (and regret) that the medical world - for whatever reason or purpose - reverts to an unmitigated, subtle mechanism of falsification which it has been built into medical statistics, thus ascribing their pretended success - which rests on nothing else but deceit - to an irrevocably mutilating surgery and an undeniable toxic (and often cancer-producing and mutagenic) chemo- and radiotherapy.
This organized statistical deceit is built in on different levels with a synergistic falsifying effect. Recapitulating :
1. Unapproachably early diagnosed cancers would entail very high chances of remission - which are held out to the outside world - and 'only' the cancers which are discovered too late are almost always fatal. The real mortality of cancer is put under the cover of late discovered cancers : 80% mortality with carcinoma of the lung, 90% mortality with stomach cancer, 98% death risk with gullet cancer, etc. It is suggested moreover, that early diagnosis will drastically curtail these mortality figures, which would in effect be true if it would be possible, as far as methods, material and technique are concerned, to make 'early diagnoses', which is not the case with current medical possibilities.
2. The counting-off of the five years' remission period - and not some treatment method success - is decisive for the longer or the shorter period of survival.
3. The medical establishment confuses willingly or knowingly 'natural' chances of survival with therapeutic successes, a favour which they refuse to acknowledge when judging extra-medical successes.
4. Borderline and dubious (quasi- and pseudo-cancers) cases are 'by way of precaution' considered more and more as cancers, and successes increase proportionally with the wrongly diagnosed cancers. And again, this is a favour which is strongly denied to the alternative treatments : a patient 'cured' by the alternative way is surely a patient who had a 'dubious' or 'unreliable' cancer diagnosis ...
5. To consider a remission of several years as free of cancer and a therapy success, when there is a good, to very good chance that a new precancerosis has begun, precisely under the influence of (mutagenic and cancerigenic) radio- or chemotherapy which will break open vehemently - though after the blessed declaration of freedom of cancer - is a last described deceitful presentation on account of medical establishment.
II. Side effects.
By this chapter we intend to provide patients and doctors in good faith with a realistic picture of the therapy successes and their side effects. For more than five years we have been sifting, exhaustively, classic medical literature, the result of which will be reflected in this chapter. It provides a realistic inside-look on chemo(toxico)therapy as it is known in medical circles, but which is carefully and systematically being conceiled extra muros. For this deliberate suppression of essential information, the medical corps appeals once more to the unemancipated position of the patient who might perhaps prefer to be treated differently, or not at all, and long for a more worthy life-ending instead of the mutilated survival ! The patient is deprived of this option in a well-orchestrated, Machiavellian way. The right to live becomes the duty to survive according to the rules of current medical art.
This chapter claims to be neither more nor less then the above. It is not intended as a systematic and pamphlet-like rejection of chemo(toxico)therapy
Instead it aims at refuting the myth that chemo(toxico)therapy would be the only efficient way to fight cancer. It is indispensable that the cancer patient knows, and realizes, that he may succumb to his chemo(toxico)therapeutic treatment, or contract a second cancer (most therapeutic agents are cancer-producing !) and that, if he is favoured with a 'survival period', he will certainly have to 'live' with numerous side effects, going from banal digestive upsets, to haemorrhage, impairment (reversible or otherwise) of the blood image, marrow, liver, bladder, lung, heart, etc., not to mention the permanent (but well-founded) fear for mutagenic and cancer-producing side effects of anti-cancer agents. Non-cancer patients may be confronted with these expected iatrogenic effects as well. Indeed, non-malignant (such as rheumatism, psoriasis) are 'treated' with such anti-cancer agents.In a period when the right to self-determination, emancipation, women's right to decide on abortion, all sorts of liberties, are in everybody's mind, it makes no sense that only the (cancer) patient would be considered and treated as unemancipated and that 'in his own interest' he would be kept ignorant about what he is up against ...
All elements must be presented to him, thus enabling him to make his own decision in a conscious way and with full knowledge of the facts - a decision of life and death, for that matter !
This chapter wants to contribute to this in an essential way by opening (for the first time?) the door to specialized medical literature, thus making it accessible to the layman.
Consequently, the patient will acquire his medical maturity and be able to prefer a short(er) (?) but worthier life (of life-ending), to a mutilated longer (?) period of survival, according to the rules of current medical art ...
As an introduction to the following survey of chemo(toxico) therapeutic drugs and their specific side effects, it is worth indicating that these drugs cover a 'broadspectrum side effects field' and the side effects of the under-mentioned categories only differ mutually as to their intensity and spread.
The side effects of drugs are generally categorized as follows, according to their 'site of
action' :
1. Digestive upsets (nausea, vomiting, anorexia, stomatitis, diarrhoea, etc.):
SCHEIN, P.S., MACDONALS, J.S., WATERS, C., HAIDAK,D., Nutritional complications of cancer and its treatment, Semin. Oncol., Dec. 1975; 2 (4): 337-347; DREIZEN, S., Stomatotoxic manifestations of cancer chemotherapy, J. Prosthet. Dent., Dec. 1978; HYSON, E.A., BURRELL, M., TOFFLER, R., Drug-induced gatrointestinal disease, Gastrointest. Radiol., 20 Dec. 1977; 2 (3): 183-212; OHNOMA, T., HOLLAND, J.F., Nutritional consequences of cancer chemotherapy and immunotherapy, Cancer Res., July 1977, 37 (7 Pt 2): 2395-2406; N.N., Cancer chemotherapy the inbuilt deterrent, Br. Med. J., 24 Nov. 1979; 2 (6201): 1312-1313; SCHUM, C.A., IZUTSU, K.T., MOLBO, D.M., TRUELOVE, E.L., GALLUCCI,B., Changes in salivary buffer capacity in patients undergoing cancer chemotherapy, J. Oral. Med., Jul-Sept., 1979; 34 (3): 76-80; SCOGNA, D.M., SMALLEY, R.V., Chemotherapy-induced nausea and vomiting, Am J. Nurs., Sept. 1979; 79 (9): 1562-1564; KENNEDY, M., PACKARD, R., GRANT, M.M., PADILLA, G.V., Chemotherapy related nausea and vomiting: a survey to identify problems and interventions, Oncol. Nurs. Forum, Winter 1981; 8 (1): 19-22.
2. Affections of the skin and mucuous membrane (all sorts of affections, nail dammage, alopecia, etc.):
NIXON, D.W, Alterations in nail pigment with cancer chemotherapy, Arch. Intern. Med., Oct. 1976; 136 (10): 1117-1118; DREIZEN, S., BODEY, G.P., RODRIGUEZ, V., McCREDIE, K.B., Cutaneous complications of cancer chemotherapy, Postgrad. Med., Nov. 1975; 58 (6): 150-158; BARAN, R., Pigmentation of the nail (chromonynchia), J. Dermatol. Surg. Oncol., Mar. 1978; 4 (3): 250-254; GAUCI, L., SERROU, B., Changes in hair pigmentation associated with cancer chemotherapy, Cancer Treat. Rep., Jan. 1980; 64 (1): 193.
3. Haematopoietic alteration (immunodepression, blood composition alteration, etc.):
JEDRZEJCZAK, W.W., SIEKIERZYNSKI, M., CZARNECKI, C., DZIUK, E., Patterns of changes in peripheral blood composition in the course of combination chemotherapy of cancer, Strahlentherapie, Nov. 1976; 152 (5): 469-476; BODEY G.P., RODRIGUEZ, V., McCREDIE, K.B., FREIREICH, E.J., Neutropenia and infection following cancer chemotherapy, Int. J. Radiat. Oncol. Biol. Phys., Jan. - Feb. 1976; 1 (3-4): 301-304; VAN DER HOEVEN, L., CHANG, J.C., Disorders of granulocytes induced by toxic agents, Ann. Clin. Lab. Sci., Sept. - Oct. 1976; 6 (5): 415-422; TATTERSHALL, M.H., Aggressive cancer treatment and its role in predisposing to infection, Eur. J. Cancer, Aug. 1975; 11 Suppl.: 9-19; RENOUX, M., BERNARD, J.F., TORRES, M., SCHLEGEL, N., AMAR, M., LOPEZ, M., BOIVIN, P., Erythrocyte abnormalities induced by chemotherapy and radiotherapy: induction of preleukemic state., Scand. J. Hematol., Oct. 1978; 21 (4): 323-332; FERRARO, E.F., Implications of antineoplastic therapy, Dent. Surv., Febr. 1978; 54 (2): 32-33; MASON, B.A., KLUG, P.P., COHEN, P., Bone marrow necrosis during chemotherapy for lymphoma, J.A.M.A., 20 Mar. 1978; 239 (12): 1158; BADHURI, S., RASHE, H., KÖHLE, W., DIETRICH, M., Blutgerinnungsstudien bei Patienten mit akuter Leukämie vor und nach zytostatischer Chemotherapie, Verh. Dtsch. Ges. Inn. Med., 17-21 Apr. 1977; 83: 1142-1144; KAKISHITA, E., YOSHIMURA, S., Influence of anticancer chemotherapy on hemostatic mechanism (Japanese), Rinsho Byori, Dec. 1977, 25 (12): 985-991; NERI, A., BRUGIATELLI, M., COMIS, M., IACOB, P., NOBILE, F., PACIUCCI, P.A., LOMBARDO, V.T., Severe acute hyperkalaemia following chemotherapy, Haematologica (Pavia), Jun. 197 ***; 62 (3): 331-332; KREPLER, P., Infections in children with malignant disease, Wien. Klin. Wochenschr., 9 Nov. 1979; 91 (21): 707-71 *** ; RYBALBA, A.M., Prevention and treatment of hemapoietic disorders during the chemotherapy of malignant ovarian tumours (Ukranian), Pedriatr. Akush. Ginekol., Sept. - Oct. 1979; (5): 45-46; ETIEMBLE, J., BERNARD, J.F., PICAT, C., BELPOMME, D., BOIVIN, P., Red blood cell enzyme abnormalities in patients treated with chemotherapy, Br. J. Haematol., Jul. 1979; 42 (3): 391-398: HAROUSSEAU, J.L., TOBELEM, G., SCHAISON, G., JACQUILLAT, C., Leucémies aigues lymphoblastiques hyperleucocytaires: problèmes d'urgence au cours du traitement initial, Nouv. Presse Méd., 19 May 1979; 8 (22): 1827-1830; LY, B., SOLHEIM, B.G., SKAR, A.G., Granulocytopenia and infections during induction therapy of acute leukemia (Norwegian), Tidsskr. Nor. Laegeforen, Febr. 1981; 101 (6): 379-386.
4. Affection of the reproductive organs (sterility, impotence, azoospermia, amenorrhea, gynecomastia, etc.):
RUSSEL, J.A., POWLES, R.L., OLIVER, R.T., Conception and congenital abnormalities after chemotherapy of acute myelogenous leukemia in two men, Br. Med. J., 19 Jun. 1976; 1 (6024): 1508; SIRIS, E.S., LEVENTHAL, B.G., VAITUKAITIS, J.L., Effects of childhood leukemia and chemotherapy on puberty and reproductive function in girls, N. Engl. J. Med., 20 May 1976; 294 (21): 1143-1146; ASBJORNSEN, G., MOLNE, K., KLEPP, O., AAKVAAG, A., Testicular function after combination chemotherapy for Hodgkin's disease, Scand. J. Haematol., Jan. 1976; 16 (1): 66-69; DI LIBERTI, J.H., Teratogenesis and chemotherapy, Ann. Intern. Med., Nov. 1974; 81 (5): 709; SUTCLIFFE, S.B., Cytotoxex chemotherapy and gonadal function in patients with Hodgkin's disease, J.A.M.A., 26 Oct. 1979; 242 (17): 1898-1899; CHAPMAN, R.M., SUTCLIFFE, S.B., MALPAS, J.S., Cytotoxic-induced ovarian failure in Hodgkin's disease. Effects on sexual function, J.A.M.A., 26 Oct. 1979; 242 (17): 1882-1884; GLASS, A.R., BERENBERG, J., Gynecomastia after chemotherapy for lymphoma, Arch. Intern. Med., Sept. 1979; 139 (9): 1048-1049; RUSTIN, G.J., BAGSHAWE, K.D., NEWLANDS, E.S., BEGENT, R.H., Cytotoxic drugs and sterility, Lancet, 13 Jun. 1981; 1 (8233): 1316; THORNELDE, W.F., Cytotoxic-induced ovarian failure in Hodgkin's disease, J.A.M.A., 1 Aug. 1980; 244 (5): 435.
5. Renal and liver insufficiency :
JAYABOSE, S., SHENDE, A., LANZKOWSKY, P., Hepatotoxicity of chemotherapy following nephrectomy and radiation therapy for right-sided Willms tumour, J. Pediatr., May 1976; 88 (5): 898; KANFER, A., ROLAND, J., CHATELET, F., RICHET, G., Insuffisance rénale aigue hyperphosphatémique au cours d'un lymphosarcome, J. Urol. Nephrol., (Paris), Apr. - May 1979; 85 (4-5): 337.
6. Impairment of the osseous system :
IHDE, D.C., DEVITA, V.T., Osteonecrosis of the femoral head in patients with lymphoma treated with intermittent combination chemotherapy, Cancer, Nov. 1975; 36 (5): 1585-1588.
7. Pulmonary diseases :
KÜHBÖCK, S., Lungenfibrosen nach Behandlung mit Zytostatika, Wien. Med. Wochenschr., 1 Oct. 1976; 126 (40): 568-570; CAUBARRERE, I., Les pneumopathies infectueuses au cours de la chimiothérapie des hémopathies malignes, Rev. Prat., 21 May 1976; 26 (29): 2051-2060; SIZOD, W., WOLVIUS, G.G., Pneumocystis-pneumonie als complicatie bij cytostatische therapie, Nederl. Tijdschr. Geneeskunde, 6 Mar. 1976; 120 (10): 418-424; SAUER, E., GULLOTTA, U., FINK, U., Akute beidseitige Lungeninfiltration als Komplikation der Zytostatischen Therapie, Dtsch. Med. Wochenschr., 10 Oct. 1975; 100 (41): 2098-2101; OKITA, H., ITO, K., TAKETOMI, Y., FUJIMURA, K., KURAMOTO, A., Four patients with leukemia who showed especially a typical type of interstitial pneumonia, probably caused following the administration of anti-leukemic drugs (Japanese), Jpn. J. Clin. Hematol., 30 Jul. 1974; 15 (7): 764-773; HERMANSKY, F., BENESOVA, E., CHMEL, J., JIRAK, A., Pulmonary complications caused by cytostatic treatment (Czech), Vnitr. Lek., Jun. 1977; 23 (7): 695-701; DEMETER, S.L., AHAMD, M., TOMASHEKSKI, J.F., Drug-induced pulmonary disease, Cleve. Clin. Q., Fall 1979; 46 (3): 113-124; ZHU, G.Y., Acute pulmonary edema during chemotherapy of late stage tumors (Chinese), Chung Hua Chieh Ho Ho Hu Hsi Hsi Chi Ping Tsa Chih, Dec. 1980; 3 (4): 201-202.
8. Mutagenic changes :
MAJSKY, A., JAKOUBKOVA, J., ABRAHAMOVA, J., Chemotherapy one of the causes of transient loss of HLA antigens and lymphocyte poly-reactivity in patients with blood diseases and malignancies, J. Immunogenet., Dec. 1976; 3 (6): 429-433; ROSS, G.T., Congenital anomalies among children born of mothers receiving chemotherapy for gestational trophoblastic neoplasms, Cancer, Feb. 1976; 37 (2 Suppl.): 1043-1047; POLEKSIC, S., YEUNG, K.Y., Rapid development of keratoancanthoma and accelerated transformation into squamous cell carcinoma of the skin: a mutagenic effect of polychemotherapy in a patient with Hodgkin's disease?, Cancer, Jan. 1978; 41 (1): 12-16; SCHAISON, G., JACQUILLAT, C., AUCLERC, G., WEIL, M., Les risques foeto-embryonnaires des chimiothérapies, Bull. Cancer (Paris), 1979; 66 (2): 165-170; SAKALOVA, A., BENKO, J., IZAKOVIC, V., Antitumorous therapy and its consequences upon gravidity and foetus (Slovakian), Cesk. Gynekol., May 1979; 44 (4): 272-276; SCHADER, A.I., Teratogenic effects of antileukemia chemotherapy, Arch. Intern. Med., Mar. 1981; 141 (4): 514-515; KAEMPFER, S.H., The effects of cancer chemotherapy on reproduction: a review of the literature, Oncol. Nurs. Forum, Winter 1981; 8 (1): 11-18.
9. Cancer-producing side effects :
HAQUE, T., LUTCHER, C., FAGUET, G., TALLEDI, O., Chemotherapy-associated acute myelogenous leukemia and ovarian carcinoma, Am. J. Med. Sci., Sept. - Oct. 1976; 272 (2): 225-228; JOCHIMSEN, P.R., PEARLMAN, N.W., LAWTON, R.L., Pancreatic carcinoma as a sequel to therapy of lymphoma, J. Surg. Oncol., 1976; 8 (6): 461-464; SEIDENFELD, A.M., SMYTHE, H.A., OGRYZLO, M.A., UROWITZ, M.B., DOTTEN, D.A., Acute leukemia in rheumatoid arthritis treated with cytotoxic agents, J. Rheumatol., Sept. 1976; 3 (3): 295-304; ROBERTS, M.M., Acute leukemia after immunosuppressive therapy, Lancet, 9 Oct. 1976; 2 (7989): 768-770; KUIS, W., DE KRAKER, J., KUIJTEN, R.H., DONCKERWOLCKE, R.A., VOUTE, P.A., Acute lymphoblastic leukemia after treatment of nephrotic syndrome with immunosuppressive drugs, Helv. Paediatr. Acta, Jun. 1976; 31 (1): 91-95; NAESS, K., Cancer of the pancreas chemically induced. Can drugs play a role? (Norwegian), Tidsskr. Nor. Laegeforen, 10 Jun. 1976; 96(16): 949; STECHMILLER, B., WIERNIK, P.H., SHIN, M., SATTERFIELD, J., Metastatic teratocarcinoma following chemotherapy. Maturation to a mass pathologically indistinguishable from a mediastinal enteric cyst, Chest, May 1976; 69 (5): 697-700; JAFFE, N., Late side effects of treatment: skeletal, genetic, central nervous system and oncogenic, Pediatr. Clin. N. Am., Feb. 1976; 23 (1): 233-244; MEADOWS, A.T., D'ANGIO, G.J., EVANS, A.E., HARRIS, C.C., MILLER, R.W., MIKE, V., Oncogenesis and other late effects of cancer treatment in children, Radiology, Jan. 1975; 114 (1): 175-180; SCHWARZ, J.H., CANELLOS, G.P., YOUNG, R.C., DEVITA, V.T. Jr., Meningeal leukemia in the blastic phase of chronic granulocytic leukemia, Am. J. Med., Dec. 1975, 59 (6): 819-829; TERRACINI, B., Il ruolo di alcuni farmaci nell'ezioologia dei tumori delle vie urinarie, Cancro, 1973; 26 (3): 185-188; LI, F.P., CASSADY, J.R., JAFFE, N., Risk of second tumors in survivors of childhood cancer, Cancer, Apr. 1975: 35 (4): 1230-1235; CARTER, S.K., Second tumors complicating cancer therapy, Haematol. Bluttransfus., 1978; 22: 41-44; BOIVIN, P., Les leucémies induites par la radiothérapie ou par la chimiothérapie peuvent-elles êtres prévues? Nouv. Presse Méd., 9 Sept. 1979; 7 (29): 2533-2534; LEGLER, F., Karzinogenese durch Schadstoffe aus der Umwelt, Pharmaka und Ernährungsgewohnheiten, Oeff. Gesundheitswes., Oct. 1978; 40 (10): 653-662; SCHULER, D., Iatrogenic carcinogenesis (Hungarian), Orv. Hetil., 10 Sept. 1978; 119 (37): 2239-2243; ROSNER, F., Is chemotherapy carcinogenic?, Cancer, Jan. Feb. 1978; 28 (1): 57-59; PENN, I., Malignancies associated with immunosuppressive or cytotoxic therapy, Surgery, May 1978; 83 (5): 492-502; NIEWEG, H.O., Iatrogene leukemie, Nederl. Tijdschr. Geneesk., 25 Mar. 1978; 122 (12): 398-401; MULDER, N.H., HOUWEN, B., Behandelen en vooruitzien. Acute leukemie na behandeling van een andere kwaadaardige ziekte, Nederl. Tijdschr. Geneesk., 25 Mar. 1978; 122 (12): 385-399; ERSKINE, J.G., WANG, I., HUTTON, M.M., Chronic granulocytic leukemia developing upon a follicular lymphoma, Br. Med. J., 19 Nov. 1977; 2 (6098): 1329; CADMAN, E.C., CAPIZZI, R.L., BERTINO, J.R., Acute non-lymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases, Cancer, Sept. 1977; 40 (3): 1280-1296; CHABNER, B.A., Second neoplasm a complication of cancer chemotherapy, N. Engl. J. Med., 28 Jul. 1977, 297 (4): 213-215; KURTIDES, E.S., Breast cancer, chemotherapy and second malignant neoplasms, J.A.M.A., 4 Jul. 1977; 238 (1): 28-29; WOLF, M.M., COOPER, I.A., DING, J.C., Hodgkin's disease terminating in acute leukemia: a report of seven cases, Austr. N. Z. J. Med., Aug. 1979; 9 (4): 398-402; KAHN, M.F., ARLET, J., BLOCH-MICHEL, H., CAROIT, M., CHAOUAT, Y., RENIER, J.C., Leucémies aigues après traitement par agents cytotoxiques en rhumatologie. 19 observations chez 2006 patients, Nouv. Presse Méd., 14 Apr. 1979; 8 (17): 1393-1397; PENN, I., Leukemias and lymphomas associated with the use of cytotoxic and immunosuppressive drugs, Cancer Res., 1979; 69: 7-13; JOUET, J.P.,HUART, J.J., BAUTERS, F., GOUDEMAND, M., Leucémies aigues complicant la maladie de Hodgkin. Cinq nouvelles observations, Nouv. Presse Méd., 17 Feb. 1979; 8 (8): 613-614; DANO, K., FORCHHAMMER, J., Carcinogenesis and drugs (Danish), Ugeskr. Laeger., Aug. 1981; 143 (35): 2246-2247; FARBER, E., Chemical carcinogenesis, N. Engl. J. Med., 3 Dec. 1981; 305 (23): 1379-1389; STEWART, A.L., WILKINSON, P.M., Rapid onset of acute myeloid leukemia following radiotherapy and chemotherapy for metastatic seminoma of the testis, J. Cancer Res. Clin. Oncol., 1981; 100 (1): 109-111; HOOVER, R., FRAUMENI, J.F., Jr., Drug-induced cancer, Cancer, 1 Mar. 1981; 47 (5 Suppl.): 1071-1080; BLANC, A.P., GASTAUT, J.A., SEBAHOUN, G., DALIVOUST, P., MURISASCO, A., CARCASSONNE, Y., Naissance d'une leucémie aigue au décours d'un traitement immunosupprésseur par le chlorambucil. Une observation, Nouv. Presse Méd., May 1981; 10 (21): 1717-1719; CORDIER, J.F., TOURAINE, R., Cancers épidermoides du poumon chez un patient traité pour cancer aplasique à petites cellules. La chimiothérapie favorise-t-elle le développement de cancers d'un autre type histologique?, Nouv. Presse Méd., 9 May 1981; 10 (21): 1713-1716; ASBORNSEN, G., GODAL, H.C., MYHRE, K., Acute myelogenous leukemia after cytostatic therapy in breast cancer (Norwegian), Tidsskr. Nor. Laegeforen, Feb. 1981; 101 (6): 387-388; PENN, I. Immunosuppression and skin cancer, Clin. Plast. Surg., Jul. 1980, 7 (3): 361-368; CHAN, K.W., MILLER, D.R., TAN, C.T., Osteosarcoma and acute myeloblastic leukemia after therapy for childhood Hodgkin's disease - a case report, Med. Pediatr. Oncol., 1980; 8 (2): 143-149; MAHOMED, Y., MANDEL, M.A., CRAMER, S.F., MICHEL, B., Squamous cell carcinoma arising in pemphigus vulgaris during immunosuppressive therapy, Cancer, 15 Sept. 1980; 46 (6): 1374-1377; DOHY, H., GENOT, J.Y., IMBERT, M., D'AGAY, M.F., SULTAN, C., Myelodysplasia and leukemia related to chemotherapy and/or radiotherapy: a haematological study of 13 cases. Value of macrocytosis as an early sign of bone marrow injury, Clin. Lab. Haematol., 1980, 2 (2): 111-119.
10. Impairment of the central nervous system :
SHERKOW, L.H., Chemotherapeutic neurotoxicity on brain scintigraphy, Clin. Nucl. Med., Oct. 1979; 4 (10): 439-440.
11. Cardiotoxicity :
KAYE, S.B., IKRAM, H., Acute cardiac pain and electrocardiographic changes following cytotoxic treatment for metastatic carcinoma, Clin. Oncol., Sept. 1976; 2 (3): 215-218; WEINSTEIN, P., GREENWALD, E.S., GROSSMAN, J., Unusual cardiac reaction to chemotherapy following mediastinal irradiation in a patient with Hodgkin's disease, Am. J. Med., Jan. 1976; 60 (1): 152-156; APPELBAUM, F., STRAUCHEN, J.A., GRAW, R.G. Jr., SAVAGE, D.D., KENT, K.M., FERRANS, V.J., HERZIG, G.P., Acute lethal carditis caused by high-dose combination chemotherapy. A unique clinical and pathological entity, Lancet, 10 Jan. 1976; 1 (7950): 58-62; GHIONE, M., Effetti tossici dei farmaci antitumorali sul sistema cardiovascolare, Recent Prog. Med. (Roma), Oct. 1977; 63 (4): 382-410; SZABO, G., KOVACS, A., Intra-arterial chemotherapy of head and neck tumours, Acta Chir. Acad. Sci. Hung., 1979; 20 (1): 49-55; GARIMOLDI, M., PIAZZA, E., BERTELLO, C., RUGGERI, P.R., LIBRETTI, A., Effetto della chemioterapia antiblastica su alcuni parametri cardiologice, Boll. Soc. Ital. Cardiol., 1978; 23 (10): 1785-1790.
12. Miscellanea :
Hansen SW; Helweg-Larsen S; Trojaborg W, Long-term neurotoxicity in patients treated with cisplatin, vinblastine, and bleomycin for metastatic germ cell cancer, J Clin Oncol (UNITED STATES) Oct 1989 7 (10) p1457-61;Eifel PJ; McClure S , Severe chemotherapy-induced recall of radiation mucositis in a patient with non-Hodgkin's lymphoma of Waldeyer's ring [letter], Int J Radiat Oncol Biol Phys Oct 1989 17 (4) p907-8; Tsatsoulis A; Shalet SM; Robertson WR; Morris ID; Burger HG; De Kretser DM, Plasma inhibin levels in men with chemotherapy-induced severe damage to the seminiferous epithelium., Clin Endocrinol (Oxf) (ENGLAND) Dec 1988 29 (6) p659-65; Ocular complications after intracarotid BCNU for intracranial tumors, Acta Ophthalmol (Copenh) Feb 1989 67 (1) p83-6; Gerasimova MM; Bogoslovskaia IA; Karcharova SV; Litovskaia AV, Professional diseases caused by the action of antibiotics, Vrach Delo (USSR) May 1989 (5) p109-12; Cartei G; Ceschia T; Marsilio P; Clocchiatti L; Fasola G; Morandini G; Galletti D; Sibau A, Effectiveness and toxicity of "BELD" polychemotherapy in advanced malignant melanoma, Tumori (ITALY) Jun 30 1989 75 (3) p229-32; Mansi ML , Clear cell renal carcinoma in a pregnant DES-exposed patient, J Am Osteopath Assoc (UNITED STATES) Jul 1989 89 (7) p929-32; Williams F, Diethylstilboestrol exposure and testicular cancer [letter], Int J Epidemiol (ENGLAND) Jun 1989 18 (2) p462-3 ISSN: 0300-5771 Language: ENGLISH; Bressollette L; Swirsky H; Kernaleguen D; Carlhant D; Fauquert P; Le Bot MA; Baccino E; Riche C, Hepatitis during treatment with tamoxifen. Effects on the kinetics of epirubicin (letter), Therapie (FRANCE) Mar-Apr 1989 44 (2) p151-2 ; Meneghello A; Presacco D; Di Maggio C, Aseptic osteonecrosis of the femoral head in cancer patients with neuropathies caused by vincristine and vinblastine] Complesso Clinico Ospedaliero, Padova. Radiol Med (Torino) (ITALY) Jun 1989 77 (6) p626-30; Grasela TH Jr; Walawander CA; Welage LS; Wing PE; Scarafoni DJ; Caldwell JW; Noguchi JK; Schentag JJ , Prospective surveillance of antibiotic-associated coagulopathy in 970 patients, Pharmacotherapy 1989 9 (3) p258-64; Rubin B; Palestine AG, Complications of corticosteroid and immunosuppressive drugs, Int Ophthalmol Clin (UNITED STATES) Fall 1989 29 (3) p159-71 ; Peiffert D; Bey P; Lederlin P; Conroy T; Witz F , Immediate hematological toxicity during combination chemotherapy- radiotherapy of Hodgkin's disease, Bull Cancer (Paris) 1989 76 (4) p373-82; Szende B; Schally AV; Srkalovic G; Comaru-Schally AM; Wittliff JL , Adverse effect of tamoxifen with LHRH agonist on oestrogen-receptor-negative mammary carcinoma [letter] , Lancet (ENGLAND) Jul 22 1989 2 (8656) p222-3; Matsuura T; Nakabayashi H; Yanagisawa T; Yamazaki K; Watanabe R; Kameda H; Sakata A , Primary malignant lymphoma of the brain following immunosuppressive therapy of systemic lupus erythematosus, Nippon Naika Gakkai Zasshi (JAPAN) May 1987 76 (5) p730-5 ; Metzler M , Metabolism of some anabolic agents: toxicological and analytical aspects, J Chromatogr (NETHERLANDS) Apr 7 1989 489 (1) p11-21; Hirvonen HE; Salmi TT; Heinonen E; Antila KJ; Valimaki IA , Vincristine treatment of acute lymphoblastic leukemia induces transient autonomic cardioneuropathy, Cancer Aug 15 1989 64 (4) p801-5; Wilkinson H , Dangers from methylprednisolone acetate therapy by intraspinal injection [letter], Arch Neurol (UNITED STATES) Jul 1989 46 (7) p721-2; Hillbertz-Nilsson K; Forsberg JG , Genotoxic effects of estrogens in epithelial cells from the neonatal mouse uterine cervix: modifications by metabolic modifiers, Teratogenesis Carcinog Mutagen (UNITED STATES) 1989 9 (2) p97-110; Gendron Y; Bronstein JA; Gras C; Boz P, Neuromuscular toxicity of colchicine. A case (letter)], Presse Med Jun 24 1989 18 (25) p1256; Hansen SW; Olsen N , Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin for germ cell cancer: measurement of vasoconstrictor response to cold, J Clin Oncol (UNITED STATES) Jul 1989 7 (7) p940-2; Boudouris O; Ferrand S; Guillet JL; Madelenat P , Paradoxical effects of tamoxifen on the woman's uterus, J Gynecol Obstet Biol Reprod (Paris) (FRANCE) 1989 18 (3) p372-8; Fillastre JP, Drug nephrotoxicity: mechanisms of action] Nephrotoxicite medicamenteuse: mecanismes d'action, Ann Biol Clin (Paris) 1989 47 (2) p91-7; Wortsman J; Hamidinia A; Winters SJ, Hypogonadism following long-term treatment with diethylstilbestrol, Am J Med Sci (UNITED STATES) Jun 1989 297 (6) p365-8; Mironova IN; Batov SV; Aldylbaev TA, Mental disorders during chemotherapy of malignant testicular neoplasms, Zh Nevropatol Psikhiatr (USSR) 1989 89 (2) p87-90; Wingard DL; Turiel J , Long-term effects of exposure to diethylstilbestrol, West J Med (UNITED STATES) Nov 1988 149 (5) p551-4; N.N., Ophthalmologic complications of low-dose tamoxifen in the treatment of breast carcinoma (letter), Ned Tijdschr Geneeskd (NETHERLANDS) Apr 29 1989 133 (17) p903-4 ; Wiest PM; Flanigan T; Salata RA; Shlaes DM; Katzman M; Lederman MM , Serious infectious complications of corticosteroid therapy for COPD, Chest (UNITED STATES) Jun 1989 95 (6) p1180-4 ; Vyborov AM; Romanenko GF , Kaposi's sarcoma in a female patient taking corticosteroids for a long time, Vestn Dermatol Venerol (USSR) 1989 (1) p48-9 ; Fujii H; Yashige H; Maekawa T; Horiike S, Acute myeloid leukemia six years after chemotherapy of Hodgkin's disease] , Rinsho Ketsueki (JAPAN) Dec 1988 29 (12) p2369-74; Beyer BK; Greenaway JC; Fantel AG; Juchau MR , Embryotoxicity induced by diethylstilbestrol in vitro, J Biochem Toxicol Summer 1987 2 p77-92 ; Love RR , Tamoxifen therapy in primary breast cancer: biology, efficacy, and side effects, J Clin Oncol (UNITED STATES) Jun 1989 7 (6) p803-15 ; von Muhlendahl KE; Bramswig J; Traupe H; Happle R, Acne fulminans following high-dose testosterone treatment in tall boys, Dtsch Med Wochenschr (GERMANY, WEST) May 5 1989 114 (18) p712-4 ; Lagler U; Gattiker HH , Acute dyspnea following intravenous administration of vinblastine/mitomycin C, Schweiz Med Wochenschr (SWITZERLAND) Mar 4 1989 119 (9) p290-2 ; de Jong-Busnac M , Ophthalmologic complications of low-dosage tamoxifen in the treatment of breast carcinoma, Ned Tijdschr Geneeskd (NETHERLANDS) Mar 11 1989 133 (10) p514-6 Peterson GM; McGinty JF , Direct neurotoxic effects of colchicine on cholinergic neurons in medial septum and striatum, Neurosci Lett Nov 22 1988 94 (1-2) p46-51; Luciani I , Fatal i.v. colchicine injection in a 60-year-old woman, JEN Mar-Apr 1989 15 (2( Pt 1)) p80-2; Zeymer U; Neuhaus KL , Infarct-typical changes in the electrocardiogram following chemotherapy with vinblastine, Dtsch Med Wochenschr (GERMANY, WEST) Apr 14 1989 114 (15) p589-92 ; Lamartiniere CA; Pardo GA , Altered activation/detoxication enzymology following neonatal diethylstilbestrol treatment., J Biochem Toxicol Summer 1988 3 p87-103; Saxena AK; Nigam PK, Panniculitis following steroid therapy, Cutis Oct 1988 42 (4) p341-2; Ochs J; Mulhern RK , Late effects of antileukemic treatment, Pediatr Clin North Am Aug 1988 35 (4) p815-33 ; LeBaron S; Zeltzer LK; LeBaron C; Scott SE; Zeltzer PM , Chemotherapy side effects in pediatric oncology patients: drugs, age, and sex as risk factors, Med Pediatr Oncol 1988 16 (4) p263-8 ; Satou M; Koshikawa S , Drug-induced glomerulonephritis, Nippon Rinsho (JAPAN) Jun 1988 46 (6) p1413-8 ; Gonadal activity and chemotherapy-induced gonadal damage [letter], JAMA (UNITED STATES) Oct 14 1988 260 (14) p2064-6; Gradishar WJ; Schilsky RL , Effects of cancer treatment on the reproductive system, CRC Crit Rev Oncol Hematol (UNITED STATES) 1988 8 (2) p153-71; Brok KE; Elberg JJ , Teratogenic effect of thiotepa despite observation of safety regulations, Ugeskr Laeger (DENMARK) Aug 1 1988 150 (31) p1898-9; Brinch L; Evensen SA; Stavem P; Svare A, Neurological problems in leukemia, Tidsskr Nor Laegeforen (NORWAY) Aug 10 1988 108 (22) p1587-9; Ries F, Nephrotoxicity of chemotherapy, Eur J Cancer Clin Oncol (ENGLAND) Jun 1988 24 (6) p951-3 ; Drings P , Late cardiorespiratory sequelae following chemo- and radiotherapy, Med Klin (GERMANY, WEST) May 27 1988 83 (12) p408-16; Smith MA; Shah NR; Lobel JS; Cera PJ; Gary GW; Anderson LJ, Severe anemia caused by human parvovirus in a leukemia patient on maintenance chemotherapy, Clin Pediatr (Phila) Aug 1988 27 (8) p383-6; Kusumoto M; Nagata M; Seguchi U , Nursing of a leukemic patient with severe nausea and vomiting caused by chemotherapy, Kango Gijutsu (JAPAN) Jun 1988 34 (8) p926-30; Bookman MA; Longo DL; Young RC , Late complications of curative treatment in Hodgkin's disease [clinical conference, JAMA (UNITED STATES) Aug 5 1988 260 (5) p680-3; Scrobohaci ML; Drouet L; Baudin B , Hemostasis tests as markers of hepatic and endothelial toxicity in chemotherapy, Nouv Rev Fr Hematol (GERMANY, WEST) 1988 30 (1-2) p109-14; Kaldor JM; Day NE; Hemminki K, Quantifying the carcinogenicity of antineoplastic drugs, Eur J Cancer Clin Oncol Apr 1988 24 (4) p703-11; Frick SB; Guzzi DelPo E; Keith JA; Davis MS, Chemotherapy-associated nausea and vomiting in pediatric oncology patients, Cancer Nurs Apr 1988 11 (2) p118-24; Madsen ES; Larsen H , Excretion of mutagens in sweat from humans treated with anti-neoplastic drugs, Cancer Lett (IRELAND) Jun 15 1988 40 (2) p199-202 ; Colls BM , Cytotoxic chemotherapy: a potential hazard to patients and hospital personnel?, N Z Med J Mar 11 1987 100 (819) p149-50; Shaw PJ; Nightingale WE; Bergin ME; Stevens MM, Use of silver sulphadiazine cream for burns caused by cytotoxic-drug extravasation [letter], Med J Aust (AUSTRALIA) Jun 20 1988 148 (12) p657; Inamatsu T , Colonic diseases due to various therapeutic agents, Nippon Rinsho (JAPAN) Feb 1988 46 (2) p451-6 ; Kamata H; Murakami A; Miyagawa N; Yasui H; Nagano H; Abe S; Ueda K; Kisida S , A case of leukoencephalopathy caused by HCFU, Gan No Rinsho May 1988 34 (6) p783-6 ; Tsai LT; Chang TT; Hwang KP; Chen TS, Clinical study of interstitial pneumonia in acute lymphoblastic leukemia children under anti-cancer therapy, Kao Hsiung I Hsueh Ko Hsueh Tsa Chih Dec 1985 1 (12) p754-60; Krasowska I; Urban M , Non-hematological side effects of cytostatic drugs used in children, Pediatr Pol (POLAND) Nov-Dec 1987 62 (11-12) p787-92 ; Kardos G; Gacs G; Solyom J; Revesz T; Kajtar P; Koos R; Schuler R , Changes in gonadal function after treatment of malignant diseases in children, Orv Hetil Mar 27 1988 129 (13) p657-8, 661-2 ; Andrykowski MA , Defining anticipatory nausea and vomiting: differences among cancer chemotherapy patients who report pretreatment nausea, J Behav Med (UNITED STATES) Feb 1988 11 (1) p59-69; Umbach GE , Carcinoma of the cervix: chemotherapy, toxicity, and survival [letter], J Clin Oncol (UNITED STATES) May 1988 6 (5) p926-7; Propert KJ; Anderson JR, Assessing the effect of toxicity on prognosis: methods of analysis and interpretation, J Clin Oncol (UNITED STATES) May 1988 6 (5) p868-70; Nasu H; Inoue Y; Nakamura J; Iizuka M; Arakawa H; Masamune O , A case of gastric cancer associated with hyperkalemia during the effective chemotherapy, Nippon Gan Chiryo Gakkai Shi (JAPAN) Dec 20 1987 22 (10) p2347-51; van der Does-van den Berg A; Hahlen K; de Vaan GA; Veerman AJ, Late sequelae of the treatment of children with acute lymphatic leukemia, Ned Tijdschr Geneeskd Mar 26 1988 132 (13) p568-71; Meadows AT , Risk factors for second malignant neoplasms: report from the Late Effects Study Group, Bull Cancer (Paris) 1988 75 (1) p125-30; Hantel A; Rowinsky EK; Donehower RC , Nifedipine and oncologic Raynaud phenomenon [letter], Ann Intern Med (UNITED STATES) May 1988 108 (5) p767; Hoshino K; Mizushima Y; Yano S; Kitagawa M , An autopsied case of pulmonary carcinoma with perforation peritonitis due to metastatic tumor necrosis at the jejunum caused by chemotherapy, Gan No Rinsho Apr 1988 34 (4) p491-6; Rado J, Electrolyte disorders caused by drugs, Orv Hetil (HUNGARY) Jan 3 1988 129 (1) p25-31; Henry-Amar M , Quantitative risk of second cancer in patients in first complete remission from early stages of Hodgkin's disease, NCI Monogr (UNITED STATES) 1988 (6) p65-72; Mulder PO; Sleijfer DT; de Vries EG; Uges DR; Mulder NH, Renal dysfunction following high-dose carboplatin treatment, J Cancer Res Clin Oncol (GERMANY, WEST) 1988 114 (2) p212-4; Martinez CL; Ciavaglia SJ; Costello PB , Adverse effects of pharmacologic agents used in the treatment of rheumatic diseases, Ear Nose Throat J (UNITED STATES) Nov 1987 66 (11) p463-6 ; Balducci L; Phillips DM; Gearhart JG; Little DD; Bowie C; McGehee RP , Sexual complications of cancer treatment, Am Fam Physician (UNITED STATES) Mar 1988 37 (3) p159-72 ; Magnenat JL; Junod AF, Pulmonary toxicity of drugs, Ther Umsch (SWITZERLAND) Dec 1987 44 (12) p949-54; Ciambellotti E; Cartia GL; Coda C , Scintigraphy of the bone marrow for the evaluation of injuries caused by antiblastic agents, Radiol Med (Torino) (ITALY) Jan-Feb 1988 75 (1-2) p78-82 ; Najean Y , The iatrogenic leukaemias induced by radio- and/or chemotherapy, Med Oncol Tumor Pharmacother (ENGLAND) 1987 4 (3-4) p245-57 ; Fraser MC; Tucker MA , Late effects of cancer therapy: chemotherapy-related malignancies, Oncol Nurs Forum (UNITED STATES) Jan-Feb 1988 15 (1) p67-77; Fillastre JP; Viotte G; Morin JP; Moulin B, Nephrotoxicity of antitumoral agents, Adv Nephrol (UNITED STATES) 1988 17 p175-218 ; Davis HP; Newlands ES; Allain T; Hegde U , Immune thrombocytopenia caused by flavone-8-acetic acid [letter], Lancet Feb 20 1988 1 (8582) p412; Zetterberg G; Bjorkholm M; Eklund AE; Farnebo LO, Acute abdominal symptoms in patients with granulocytopenia--a clinical dilemma, Lakartidningen (SWEDEN) Dec 9 1987 84 (50) p4248-9; Ono J; Nohara T; Nakase A, Effects of anticancer drugs on hepatic fibrosis in the rats with carbon tetrachloride-induced hepatic injury, Nippon Gan Chiryo Gakkai Shi (JAPAN) Jul 20 1987 22 (6) p1240-9; Talbot GH; Provencher M; Cassileth PA, Persistent fever after recovery from granulocytopenia in acute leukemia, Arch Intern Med Jan 1988 148 (1) p129-35; Rubin RH , Empiric antibacterial therapy in granulocytopenia induced by cancer chemotherapy, Ann Intern Med (UNITED STATES) Jan 1988 108 (1) p134-6; Ivlev AS; Polunina TE, Drug-induced hepatitis during the hormonal treatment of patients with prostatic tumors, Urol Nefrol (Mosk) (USSR) Sep-Oct 1987 (5) p65-6; Kantarjian HM; Keating MJ, Therapy-related leukemia and myelodysplastic syndrome, Semin Oncol (UNITED STATES) Dec 1987 14 (4) p435-43; Tucker MA; Coleman CN; Cox RS; Varghese A; Rosenberg SA , Risk of second cancers after treatment for Hodgkin's disease, N Engl J Med (UNITED STATES) Jan 14 1988 318 (2) p76-81;D'ARCY, P.F., Iatrogenic didease: a hazard of multiple drug therapy, R. 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Belg., 1975; 30 (6): 538-546; GÜRTLER, R., The risk of adjuvant chemotherapy, Arch. Geschwulstforsch., 1978; 48 (7): 644-652; PETRANYI, G. Hazards of cytotoxic therapy (Hungarian), Orv. Hetil., 8 Jan. 1978; 119 (2): 63-69; GEIB, K.R., PAPAZIAN, R., Therapeutic progress and iatrogenic problems in malignant hemopathies (Rumanian), Rev. Med. Intern., Jul. - Aug. 1977; 29 (4): 343-349; CREAVEN, P.J., MIHICH, E., The clinical toxicity of anticancer drugs and its prediction, Semin. Oncol., Jun. 1977; 4 (2): 147-163; GUTJAHR, P., JUNG, H., Spätfolgen der Tumorbehandlung im Kindesalter, Laryngol. Rhinol. Otol. (Stuttgart), Jun. 1977; 147-163; SCHÖNFELDER, M., Komplikationen nach Chemotherapie solider maligner menschlicher Tumoren und deren Therapie, Zentralbl. Chir., 1979; 104 (17): 1103-1110; DEMIN, A.A., SMIRNOV, V.V., Chemotherapy of lymphogranulomatosis (Russian), Sov. Med., Aug. 1979; (8): 86-90; SPIEGEL, R.J., MAGRATH, I.T., Tumor lysis pancreatitis, Med. Pediatr. Oncol., 1979; 7 (2): 169-172; METTLER, F.A. Jr., Manifestation of drug toxicity, Curr. Probl. Diagn. Radiol., Jul. - Aug. 1979; 8 (4): 1-55; TULLY, J.L., LEW, M.A., CONNOR, M., D'ORSI, C.J., Clostridial sepsis following hepatic arterial infusion chemotherapy, Am. J. Med., Oct. 1979; 67 (4): 707-710; THOMSON, L., Cancer chemotherapy: a guide for nurses. Side-effects of chemotherapy, Nurs. Times, 19 Jul. 1979; 75 (29): Suppl. 5-8; HARRINGTON, W.J., Iatrogenic disorders from cancer treatment, Adv. Intern. Med., 1979; 24: 141-155; NINANE, J., Serious infections during continuing treatment of acute lymphoblastic leukemia, Arch. Dis. Child., Nov. 1981; 56 (11): 841-844; DODD, M.J., DODD, D.W., Chemotherapy: helping patients to know the drugs they are receiving and their possible side effects, Cancer Nurs., Aug. 1981; 4 (4): 311-318; GLASS, A., WIESAND, H.S., FISCHER, B., REDMOND, C., LERNER, H., WOLTER, J., SHIBATA, H., PLOTKIN, D., FOSTER, R., MARGOLESE, R., WOLMARK, N., Acute toxicity during adjuvant chemotherapy for breast cancer: The National Surgical Adjuvant Breast and Bowel Project (NSABP), experience from 1717 patients receiving single and multiple agents, Cancer Treat. Rep., May - Jun. 1981; 65 (5-6): 363-376; ZAJICEK, G., The risk of chemotherapy, Med. Hypotheses, Mar. 1981; 7 (3): 363-372; RHOMBERG, W., Probleme der kumulativen Toxizität von Radiotherapie und zytostatischer Chemotherapie beim Bronchialkarzinom, Onkologie, Jun. 1980; 3 (3): 97-101; LEVITT, D.Z., Cancer chemotherapy: those dreaded side effects and what to do about them, R.N., Aug. 1980; 43 (8): 51-54, 55-60; GHIONE, M., Effetti collaterali della chemioterapia antitumorale, Minerva Med., 14 Apr. 1980; 71 (15): 1095-1099; KAPADIA, S.B., KRAUSE, J.R., ELLIS, L.D., PAN, S.F., WALD, N., Induced non-lymphocytic leukemia following long-term chemotherapy: a study of 20 cases, Cancer, 15 Mar. 1980; 45 (6): 1315-1321; MARKOE, A.M., The effects of combined radiation and chemotherapy on the immune response, Prog. Exp. Tumor Res., 25: 219-228.
III.- Survey of the most commonly used chemo(toxico)therapeutic drugs and their specific side effects.
The introduction of cytotoxic chemical drugs into the (classic) therapeutic arsenal took place quite recently and may be traced back to the discovery, after World War II, of the anti-tumour effect of nitrogen mustard {methyl-bis (chloorethylamine), (NSC, 762, CIBA, BOOTS}. The aim of these (toxico)chemotherapeutic drugs was, and still is, to kill cancer cells left in tumours that can only partly, or not at all, be operated and/or irradiated; cancer cells left after surgical intervention; or those arrived in the bloodstreams. The absolute elimination of cancer cells remains the ultimate goal of chemo(toxico)therapy. According to the academic-medicine point of view, complete remission can only be realized of a 1 1 cancer cells are removed or killed. Consequently, the purpose is to eliminate a maximum number of cancer cells, even if this means the inevitable killing of a number of healthy cells. The chemo(toxico)therapeutic drugs (known so far) are not selective and destroy both sound and malignant cells. Therefore, they are cytotoxic (cell toxic) rather than tumour toxic. Throughout this work, we will contradict the assumption that cancer (disease) will be destroyed (the so-called regeneratio ad integrum). As a matter of fact, more and more classic cancer researchers now start to dispute the belief in the efficiency of cancer cell destruction as the optimal way of curing cancer (12).
Whilst compiling this survey our major concern was to give the reader the clearest view possible of what is being concealed by the medical establishment. Therefore we have searched and reflected on the medical literature worlwide so that the reader is aware that the bibliographic examples we have selected represent merely the tip of a massive iceberg of what is being written in medical circles about chemo(toxico) therapeutics. The contents of these articles is of less importance to the reader as, in the majority of cases, the titles are more then self-expanatory.
The enumeration is far from complete and covers in the main short periods of time within the years mentioned. The proportion of medical articles on this subject that we have quoted is infinitesimally small and the anthology that is currently being presented is only a small fraction of the literature about the harmful side effects of the 'remedies', compared to what has been published on the subject.
It is enough to envisage the cancer-producing effects of these drugs to urge the utmost caution, not to say suspicion, about this deadly therapeutic arsenal and those doctors who stubbornly promote it.
"There is only one disease of which doctors can always cure us: our credulity with respect to them" (J. Petit-Senn).
Synopsis.
1. Polyfunctional alkylating substances.
1.1. The nitrogen-musterd derivatives
1.1.1. CHLORMETHINE
1.1.2. CHLORAMBUCIL
1.1.3. MELPHALAN
1.1.4. CYCLOPHOSPHAMIDE
1.1.5. PREDNIMUSTINE1.2. Methanesulphonates:
1.2.1. BUSULPHAN
1.2.2. TREOSULFAN1.3. Ethylenimine-group
1.3.1. TRIETHYLENEMELAMINE
1.3.2. TRIETHYLENE(THIO)-PHOSPHORAMIDE1.4. MITOTANE (orthopara-DDD)
1.5. PROCARBAZINE
1.6. DACARBAZINE
1.7. CIS-PLATINUM
1.8. MANNOMUSTINE
1.9. HEXAMETHYLMELAMINE
1.10 TRETAMINE
1.11. TROFOSFAMIDE
1.12. IFOSFAMIDE
1.13. MITOCLOMINE
2. Antibiotics.
2.1. CACTINOMYCINE
2.2. DACTINOMYCINE
2.3. DAUNOMYCINE or DAUNORUBICINE
2.4. DOXORUBICINE
2.5. ADRIAMYCINE
2.6. MITTHRAMYCINE
2.7. MITOMYCINE D
2.8. QUINACRINE
2.9. PUROMYCINE
2.10. BLEOMYCINE
2.11. STREPTONIGRIN (METHYLESTER)
2.12. RUFOCROMOMYCINE
2.13. STREPTOMYCINE
2.14. PROFINOMYCINE
2.15. EPIRUBICINE
2.16. MITOXANTRON
2.17. PLICAMYCINE
2.18. STREPTOZOCINE
2.19. ZORUBICINE
2.20. ZINOSTATIN
2.21. ACLARUBICIN
3. Antimetabolics.
3.1. Folic acid antagonists
METHOTREXATE
3.2. Purine antagonists
3.2.1. 6-MERCAPTOPURINE
3.2.2. 6-THIOGUANINE
3.2.3.1. VIDARABINE (ARA A)
3.2.3.2. CYTARABINE (ARA C)
3.2.3.3. AZACITIDINE
3.2.4. DIC
3.2.5. THIOINOSIDE
3.2.6. AZATHIOPRINE
3.3. Pyrimide and nucleic acid antagonists
3.3.1.1. FLUOROURACIL
3.3.1.2. TEGAFUR
3.3.1.3. FLOXURIDINE
3.3.2. 6-AZAURACIL
3.3.3. 6-AZAURIDINE
3.3.4. 3-DEAZAURIDINE
3.3.5. 5-AZACYTIDINE
3.4. Glutamin antagonists
3.4.1. AZASERINE
3.4.2. D.O.N.
3.5. CYTEMBENA
4.Vegetal alkaloids
4.1. VINCRISTINE
4.2. VINBLASTINE
4.3. VINDESINE
4.4. VINGLYCINATE
4.5. VINLEUROSINE
4.6. VINROSIDINE
4.7. VINZOLIDINE
4.8. Epipodophylotoxines
4.8.1. TENIPOSIDE (VM 26)
4.8.2. VP 16 213 (EPE) (ETOPOSIDE)
4.8.3. PODOPHYLIN-DERIVATIVE
4.9. COLCHICINE
5. Cytotoxic substances with varied structure and action.
5.1. L-ASPARAGINASE (COLASPASE).
5.2. HYDROXYUREA
5.3. MITOGUAZONE
5.4. RAZOXANE
5.5. Nitrosol preparations.
5.5.1. CARMUSTINE (B.C.N.U.)
5.5.2. LOMUSTINE (C.C.N.U.)
5.5.3. METHYL C.C.N.U. (SEMUSTINE)
5.5.4. STREPTOZOCINE
5.5.5. NIMUSTINE
5.5.6. MUSTINE
5.5.7. URAMUSTINE
5.6. PIPOBROMAAN
5.7. PIPOSULFAAN
5.8. DIBROMOMANNITOL
5.9. ESTRAMUSTINE
5.10. ETOGLUCID
6. Miscellanea
6.1. MITOBRONITOL
6.2. MITOCLOMINE
6.3. MITOCROMINE
6.4. MITOGILLINE
6.5. MITOLACTOL
6.6. MITOMALCINE
6.7. MITOPODOZINE
6.8. QUINACRINE
6.9. 6-AMINOCHRYSEEN
6.10. ALTRETAMINE
6.11. AMSACRINE
7. Hormones and anti-hormones.
7.1. PREDNISONE
7.2. PREDNISOLONE
7.3. METHYLPREDNISOLONE
7.4. TRIAMCINOLONE
7.5. DEXAMETHASONE
7.6. BETAMETHASONE
7.7. PARAMETHASONE
7.8. TESTOSTERONEPROPRIONAAT
7.9. TESTOSTERONEOENANTHAAT
7.10. FLUOXYMESTERONE
7.11. DROSTANALONEPROPRIONAAT
7.12. DELTA-1-TESTOLOLACTONE
7.13. CALUSTERONE
7.14. DIETHYLSTILBŒSTROL (DES)
7.15. DIHYDRO-DIFENYL-HEXADIEEN-DIENŒSTROL
7.16. CHLOROTRIANISEEN
7.17 ETHYNILŒSTRADIO
7.18. TAMOXIFEEN
7.19. PRO
7.20. MEDROXYPROGESTERONE
7.21. CHLOORMADINONE
7.22. MEGESTROL
7.23. NORETHINDRONE
7.24. LIOTHYRONINE
1. Polyfunctional alkylating substances.
Alkylating substances are electrophylic substances (or can induce electrophylic substances in vivo) binding to those parts of other molecules which are rich in electrons. As they are usually not fat soluble they can hardly move through the cell membrane. Therefore, their intracellular penetration is presumed to be due to one or more transport systems which are typical of all alkylating agents (13). The alkylating agents can bind to many cell substances, proteins and nucleic acids. It is assumed however that their point of application is the DNA and that precisely the induced reactions in this respect are responsible for cell poisoning.
The following agents are distinguished in this group :
1.1. The nitrogen-mustard derivatives.
1.1.1. CHLOORMETHINE (HN2)
(MECHLORETHAMINE HCL)Chemical denomination: dichloro-2, 2N-methyl-diethylamine
Brands: CARYOLYSINE ® (Delagrange), CLORAMIN ® (Simes), DICHLOREN ® (Ciba), DIMITAN ®, (Ankerwerk), ERASOL ® (Ferrosan), MUSTARGEN ® Hcl (M.S.D.), ONCO-IMINE ® (Simes, Brussel), MUSTINE ® Hcl (Boots), CHLORMETHINUM® (INN*), MITOXINE®, MECHLORETHAMINE®.
_______________
*International Non-Proprietory Name
Side effects: (14)1. Digestive upsets: nausea, vomiting
2. Skin affections: maculopapular skin affection, skin necrosis after extravasation.
SANCHEZ YUS, E., SURAREZ MARTIN, E., Urticaria de contacto y reaccion anafilactoide inducidas por aplicacion topica de mostaza nitrogenada, Actas Dermosifiliogr., Jan. - Feb. 1977; 68 (12): 39-44; KOPF, A.W., BART, R.S., Development of more keratoancanthomas following skin testing with nitrogen mustard in a patient with the multiple keratoacanthoma syndrome, J. Dermatol. Surg. Oncol., Jun. 1979; 5 (6): 450-451; GUILHOU, J.J., BARNEON, G., MALBOS, S., PEYRON, J.L., MICHEL, B., MEYNADIER, J., Mucinose folliculaire perforante et hypersensibilité immédiate à la méchloréthamine chez un malade atteint de mycosis fongoide, Ann. Dermatol. Venereol., Jan. - Feb. 1980; 107 (1-2): 59-62; CONSTANTINE, V.S., FUKS, Z.Y., FARBER, E.M., Mechlorethamine desensitization in therpay for mycosis fungoides. Topical desensitization to mechlorethamine (nitrogen mustard) contact hypersensitivity, Arch. Sermatol., Apr. 1975; 111 (4): 484-488; SHELLY, W.B., Focal contact sensitivity to nitrogen mustard in lesions of cutaneous T-cell lymphoma (mycosis fungoides), Acta Derm. Venereol. (Stockholm), 1981; 61 (2): 161-164.
3. Impairment of the haematopoiesis: bone marrow depression, thromboflebitis, increased tendency of bleeding and infection.
4. Affection of the reproductive organs: sterility, azoospermia, amenorrhea.
5. Mutagenic effects: chromosal aberrations
6. Carcinogenetic side effects:
KRAVITS, P.H., McDONALD, C.J., Topical nitrogen mustard induced carcinogenesis, Acta Dermatol. Venereol. (Stockholm), 1978; 58 (5): 421-425; BENNET, E.J., SCHMIDT, G.B., PATEL, K.P., GRUNDY, E.M., Muscle relaxants myasthenia and mustards?, Anestesiology, Mar. 1977; 46 (3): 220-221; CARPENTIERI, U., GUSTAVSON, L.P., LOCKHART, L.H., HAGGARD, M.E., Adverse reaction to nitrogen mustard therapy, J. Pediatr., Jun. 1976; 88 (6): 1064; HARTMANN, D.W., ROBINSON, W.A., MANGALIK, A., GLODE, L.M., TRIEBEL, F., Unanticipated side-effects from treatment with high-dose mechlorethamine in patients with malignant melanoma, Cancer Treat. Rep., Mar. - Apr. 1981; 65 (3-4): 327-328.
7. Miscellanea:
Cautions in the use of herbal remedies during pregnancy and for small children [letter], Talalaj S; Czechowicz A Med J Aust (AUSTRALIA) Jan 1 1990 152 (1) p52; Rytomaa I; Meurman JH; Franssila S; Torkko H , Oral hygiene products may cause dental erosion, Proc Finn Dent Soc (FINLAND) 1989 85 (3) p161-6;
1.1.2. CHLORAMBUCIL (CLB)
Chemical denomination: P-bis- (ß-chloroethyl)-amino-fenyl) butiric acid. (NSC 3088).
Action: damages cells in mitosis by fragmentation of nucleochromosomes.
Brands: AMBOCLORIN ® (Simes), CHLORAMINOPHENE ® (Techni Pharma), LEUKERAN ® (Burroughs Wellcome), LINFOLYSIN ® (I.S.M.), CHLORAMBUCILUM® (INN).
Side effects:
1. Digestive upsets: over 15 mg/d.
2. Immuno and bone marrow depression: irreversible.
RUDD, P., FRIES, J.F., EPSTEIN, W.V., Irreversible bone-marrow failure with chlorambucil, J. Rheumatol., Dec. 1975; 2 (4): 421-429; TULLIEZ, M., RICARD, M.F., JAN, F., SULTAN, C., Preleukemic abnormal myelpoieisis induced by chlorambucil: a case study, Scand. J. Haematol., 1974; 13 (3): 179-183; STEIGBIGEL, R.T., KIM, H., POTOLSKY, A., SCHRIER, S.L., acute myeloproliferative disorder following long-term chlorambucil therapy, Arch. Intern. Med., Oct. 1974; 134 (4): 728-731; KREL, A.A., TRIFONOV, Iu. I, BOLOTIN, E.V., KANEVSKAYA, M.Z., Cytopenic syndrome in rheumatoid arthritis patients treated with leukeran and azathioprine (Russian), Sov. Med., Sep. 1979; (9): 68-72; FERME, F., ANDRIEU, J.M., BERNARD, J., Sezary syndrome occurring ten years after monoclonal gammapathy treated for four years by chlorambucil, Leuk. Res., 1981; 5 (2): 169-171.
3. Impairment of the reproductive organs:
CALLIS, L., NIETO, J., VILA, A., RENDE, J., Chlorambucil treatment in minimal lesion nephrotic syndrome: a reappraisal of its gonodal toxicity, J. Pediatr., Oct. 1980, 97 (4): 653-656.
4. Pulmonary disease:
COLE, S.R., MYERS, T.J., KLATSKY, A.U., Pulmonary disease with chlorambucil therapy, Cancer, Feb. 1978; 41 (2): 455-459; GODARD, P., MARTY, J.P., MICHEL, F.B., Interstitial pneumonia and chlorambucil, Chest, Oct. 1979; 76 (4): 471-473; LANE, S.D., BESA, E.C., JUSTH, G., JOSEPH, R.R., Fatal interstitial oneumonitis following high-dose intermittent chlorambucil therapy for chronic Lymphocyte leukemia, Cancer, 1 Jan. 1981; 47 (1): 32-36.
5. Mutagenic effects:
WESTIN, J., Chromosome abnormalities after chlorambucil therapy of polycythaemia vera, Scand. J. Haematol., Sep. 1976; 17 (3): 197-204; HERVET, E., BARRAT, J., DARBOIS, Y., FAGUER, C., Effets tératogênes des médicaments, Nouv. Presse Méd., 2 Nov. 1974; 3 (37): 2419.
6. Cancer-producing side effects:
STACHOWIAK, J., GORIN, N.C., NAJMAN, A., DUHAMEL, G., Leucémies aigues après traitement prolongé par le chlorambucil: étude de 2 cas, Ann. Méd. Interne (Paris), Aug. - Sep. 1976; 127 (8-9): 584-589; CAZALIS, M., ZITTOUN, R., KAHN, M.F., SEZE, S., Un risque particulier au traitement immunodépresseur prolongé: un cas de leucémie aigue myélo-monocytaire après traitement par le chlorambucil d'une polyarthrite rhumatoide sévère, Rev. Rhum. Mal. Osteoartic., Jun. 1976; 43 (6): 431-435; WESTBERG, N.G., SWOLIN, B., Acute myeloid leukemia appearing in two patients after prolonged continuous chlorambucil treatment for Wegener's granulomatosis, Acta Med. Scand., 1976; 199 (5): 373-377; MENKES, C.J., LEVY, J.P., WEILL, B., DELRIEU, F., MATHIOT, C., DELBARRE, F., Leucémie aigue à mégacaryoblastes survenue après traitement immunodépresseur d'une polyarthrite rhumatoide, Nouv. Presse Med., 22 Nov. 1975; 4 (40): 2869-2871; LERNER, H.J., Acute myelogenous leukemia in patients receiving Chlorambucil as long-term adjuvant chemotherapy for stage II breast cancer, Cancer Treat. Res., Aug. 1978; 62 (8): 1135-1138; WITZ, F., LEDERLIN, P., AYMARD, J.P., THIBAUT, G., GUERCI, D., Leucémies aigues myéloblastiques après traitement par chlorambucil. Deux nouveaux cas, Nouv. Presse Med., 1-8 Jul. 1978; 7 (27): 2392; FIERE, D., FELMAN, P., VU VAN, H., COIFFIER, B., Leucémies aigies myéloides après administration de chlorambucil. Deux observations, Nouv. Presse Méd., 4 Mar. 1978; 7 (3): 756; MORRISON, J., YON, J.L., Acute leukemia following chlorambucil therapy of advanced ovarian and fallopian tube carcinoma, Gynecol. Oncol., Feb. 1978; 6 (1): 115-120; CAMERON, S., Chlorambucil and leukemia, N. Engl. J. Med., 5 May 1977; 296 (18): 1065; QUEISSER, W., KALB, M., Zweitkarzinome: eine Komplikation der zytostatischen Therapie?, Med. Klin., 5 Oct. 1979; 74 (40): 1422-1430; ZIMONYI, I., CZIRBESZ, Z., DOZSA, M., Acute myeloid leukemia occuring after nephrotic syndrome treated with leukeran (Hungarian), Orv. Hetil., 7 Jan. 1979; 120 (1): 37-38; DUMONT, J., THIERY, J.P., MAZABRAUD, A., NATALI, J.C., TRAPET, P., VILCOQ, J.R., Acute myeloid leukemia following non-Hodgkin's lymphoma: danger of prolonged use of chlorambucil as maintenance therapy, Nouv. Rev. Fr. Hématol., Dec. 1980; 22 (4): 391-404; BERK, P.D., GOLDBERG, J.D., SILVERSTEIN, M.N., WEINFELD, A., DONOVAN, P.B., ELLIS, J.T., LANDAW, S.A., LASZLO, J., NAJEAN, Y., PISCIOTTA, A.V., WASSERMAN, L.R., Increased incidence of acute leukemia in polycythemia vera associated with clorambucil therapy, N. Engl. J. Med., 19 Feb. 1981; 304 (8): 441-447; AYMARD, J.P., FRUSTIN, J., WITZ, F., COLOMB, J.N., LEDERLIN, P., HERBEUVAL, R., Acute leukemia after prolonged chlorambucil treatment for non-malignant disease: report of a new case and literature survey, Acta Haematol. (Basel), 1980; 63 (5): 283-285; NAJMAN, A., GORIN, N.C., DUHAMEL, G., ROGER, M., DRY, J., Myélofibrose aigue après traitement prolongé d'une sclerose en plaques par le chlorambucil, Nouv. Presse Méd, 21 Jun. 1980; 9 (27): 1897; LEBRANCHU, Y., DRUCKER, J., NIVET, H., ROLAND, J.C., GRENIER, B., LEJARS, O., LAMAGNERE, J.P., BURIOT, D., Acute myeoblastic leukemia in child receiving chlorambucil for juvenile rheumatoid arthritis, Lancet, 22 Mar. 1980; 1 (8169): 649.
7. Impairment of the central nervous system:
SPONZILLI, E.E., SMITH, J.K., MALAMUD, N., McCULLOCH, J.R., Proggressive multifocal leukoencephalopathy: a complication of immunosuppressive treatment, Neurology (Minneap.), Jul. 1975; 25 (7): 664-668; SANDLER, R.M., GONSALKORALE, M., Chronic lymphatic leukemia, chlorambucil and sensorimotor peripheral neuropathy, Br. Med. J., 12 Nov. 1977; 2 (6097): 1265-1266; AMMENTI, A., REITTER, B., MULLER-WIEFEL, D.E., Chlorambucil neurotoxicity: report of two cases, Helv. Paediatr. Acta, Jul. 1980; 35 (3): 281-287.
8. Miscellanea:
Kaldor JM; Day NE; Pettersson F; Clarke EA; Pedersen D; Mehnert W; Bell J; Host H; Prior P; Karjalainen S; et al , Leukemia following chemotherapy for ovarian cancer, N Engl J Med (UNITED STATES) Jan 4 1990 322 (1) p1-6; Comment in: N Engl J Med 1990 Jan 4;322(1):52-3; Thompson-Moya L; Martin T; Heuft HG; Neubauer A; Herrmann R , Allergic reaction with immune hemolytic anemia resulting from chlorambucil, Am J Hematol (UNITED STATES) Nov 1989 32 (3) p230-1; N.N., The Hamman-Rich syndrome following treatment of lymphoma with chlorambucil, J. LA State Med. Soc., Aug. 1975; 127 (8): 311-315; NAJMOWICZ, D., ABROWA, H., Serious infectious complications of chronic lymphatic leukemia (Polish), Wiad. Lek., 1 Oct. 1974; 27 (19): 1743-1746; NAYSMITH, A., ROBSON, R.H., Focal fits during chlorambucil therapy, Postgrad. Med. J., Nov. 1979; 55 (649): 806-807; LEWIS, E.J., Chlorambucil for childhood nephrosis: a word of caution, N. Engl. J. Med., 24 Apr. 1980, 302 (17): 963-964.
1.1.3. MELPHALAN
Chemical denomination: p-bis (ß-chloroethylamino)-pheny-lalanine, L-4-N, N bis-2-chloroethylamino-phenylalanine,
or: L-PAM
or: L-sarcolysine (NSC 8806).Action: through alkylation of the nucleic acid of chromosomes of proliferating cells (as 1.1.2).
Brands: ALKERAN ® (Burroughs Wellcome), SARKOLYSIN ® (U.S.S.R), MELPHALANUM® (INN), ALKERANA® (Arg.).
Side effects:
1. Digestive upsets: vomiting, nausea
2. Impairment of the haematopoiesis: reversibele bone marrrow depression with anaemia, leucopenia (mainly neutropenia), bleeding.
VORONKO, E.A., FRADKIN, S.Z., Blood changes in hyperthermic perfusion with chepotherapeutic preparations (Russian), Vopr. Onkol., 1974; 20 (1): 98; SKEHAN, M.W., BERNATH, A.M., Vaculitis and Melphalan, J.A.M.A., 15 Dec. 1978; 240 (25): 2733-2734; RINGBORG, U., LEWENSOHN, R., Factors responsible for bone marrow toxicity after treatment of myeloma patients with different alkylating agents, Acta Med. Scand., 1978; 203 (4): 276-278; MORLOCK, G., BATAILLE, R., SANY, J., SERRE, H., Anémie réfractaire avec myéloblastose partielle au cours d'un myélome multiple traité par melphalan, Sem. Hop. Paris, 9-16 Apr. 1977; 53 (14-15): 853-856; PATIL, S.R., CORDER, M.P., JOCHIMSEN, P.R., DICK, F.R., Bone marrow chromosome abnormalities in breats cancer in patients following adjuvant chemotherapy, Cancer Res., Nov. 1980; 40 (11): 4076-4080.
3. Pulmonary disease:
VON EYBEN, F., OLSEN, T.S., Cytomegalovirus pneumonia after treatment with melphalan and prednisone? Report of a case, Acta Med. Scand., 1978; 203 (4): 333-335; SPANEDDA, R., ROMANINI, D., CINOTTI, A., Aspetti evolutivi di alcuni quadri di patologia polmonare in corson di emopatie croniche (correlazione con trattamento citostatico), Riv. Emoter. Immunoematol., 1979; 26 (1-2): 30-38; GOUCHER, G., ROWLAND, V., HAWKINS, J., Melphalan-induced pulmonary interstitial fibrosis, Chest, Jun. 1980; 77 (6): 805-806; WESTERFIELD, B.T., MICHALSKI, J.P., McCOMBS, C., LIGHT, R.W., reversible Melphalan-induced lung damage, Am. J. Med., May 1980; 68 (5): 767-771.
4. Impairment of the reproductive organs: sterility.
5. Cancer-producing:
BAECLAY, W.R., Multiple myeloma, melphalan and neoplasia, J.A.M.A., 4 Oct. 1976; 236 (14): 1612; BELL, R., SULLIVAN, J.R., FONE, D.J., HURLEY, T.H., Carcinoma of the breast. Occurence after treatment with melphalan for multiple myeloma, J.A.M.A., 4 Oct. 1976; 236 (4): 1609-1610; FISHMAN, S.A., RITZ, N.D., Erythroleukemia following melphalan therapy for multiple myeloma, N.Y. State J. Med., Nov. 1975; 75 (13): 2402-2404; VÖTGLI, W., NAGEL, A., BIANCHI, L., TRUOG, P., Akute myeloische Leukämie nach Alkeran-Therapie einer IgA-Paraproteinämie, Schweiz. Med. Wochenschr., 4 Jan. 1975; 105 (1): 27-28; KYLE, R.A., PIERRE, R.V., BAYRD, E.D., Multiple myeloma and acute leukemia associated with alkylating agents, Arch. Intern. Med., Jan. 1975; 135 (1): 185-192; TAETLE, R., DICKMAN, P.S., FELDMAN, P.S., Pulmonary histopathologic changes associated with melphalan therapy, Cancer, Sep. 1978; 42 (3): 1239-1245; DE BOCK, R.F., PEETERMANS, M.E., Erythroleukemia and sarcolysine, Acta Clin. Belg., 1978; 33 (1): 23-29; EINHORN, N., Acute Leukemia after chemotherapy (melphalan), Cancer, Feb. 1978; 41 (2): 444-447; MAYANS, J., REDON, J., BADIA, L., HERRANZ, C., CALABUIG, J.R., SANZ, M.A., SOLER, A., CABALLERO, M., MARTY, M.L., Mieloma multiple con transformacion a leucemia aguda, Sangre (Barcelona), 1977; 22 (6): 1026-1029; BLYTHE, J.C., Acute leukamia after melphalan treatment for ovarian carcinoma, J. Med. Assoc. State Ala., Nov. 1977; 47 (5): 42-43, 57; DE BOCK, PEETERMANS, M.E., Leukemia after prolonged use of melphalan for non-malignant disease, Lancet, 4 Jun. 1977; 1 (8023): 1208-1209; CLEMENT, F., Les hémopathies malignes induites. Six nouvelles observations dont l'une avec survie de 45 mois, Schwein. Med. Wochenschr., 14 Apr. 1979; 109 (15): 544-551; SHETTY, M.R., FREEL, R., Therapy-linked leukemia: a case report, Gynecol. Oncol., Apr. 1979; 7 (2): 264-266.
6. Miscellanea:
Zuazu I; Brunet S; Fernandez MT; Domingo-Albos A, Hepatic veno-occlusive disease in a patient undergoing bone marrow autotransplant after busulfan and melphalan conditioning (letter), Med Clin (Barc) (SPAIN) Jan 27 1990 94 (3) p119; Gertz MA; Kyle RA , Acute leukemia and cytogenetic abnormalities complicating melphalan treatment of primary systemic amyloidosis, Arch Intern Med (UNITED STATES) Mar 1990 150 (3) p629-33; Liote H; Gauthier JF; Prier A; Gauthier-Rahman S; Kaplan G; Akoun G , Acute, reversible, interstitial pneumopathy induced by melphalan], Rev Mal Respir (FRANCE) 1989 6 (5) p461-4 ; Kaldor JM; Day NE; Pettersson F; Clarke EA; Pedersen D; Mehnert W; Bell J; Host H; Prior P; Karjalainen S; et al , Leukemia following chemotherapy for ovarian cancer, N Engl J Med (UNITED STATES) Jan 4 1990 322 (1) p1-6 ; Comment in: N Engl J Med 1990 Jan 4;322(1):52-3 ; Gabrail NY , Acute leukemia after adjuvant chemotherapy for breast cancer, Mo Med (UNITED STATES) Oct 1989 86 (10) p689-90; Abe K; Imamura N; Mtasiwa DM; Inada T; Fujimura K; Kuramoto A , Multiple myeloma following chronic neutrophilia terminated with acute monocytic leukemia (AML, M 5 b), Rinsho Ketsueki (JAPAN) Jun 1989 30 (6) p910-4;Einhorn N; Eklund G; Lambert B , Solid tumours and chromosome aberrations as late side effects of melphalan therapy in ovarian carcinoma, Acta Oncol (SWEDEN) 1988 27 (3) p215-9; Morstyn G; Campbell L; Souza LM; Alton NK; Keech J; Green M; Sheridan W; Metcalf D; Fox R, Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy, Lancet (ENGLAND) Mar 26 1988 1 (8587) p667-72; Lauta VM; Valerio G; Greco A; Capece Minutolo M, Early-onset diagnosis of lung toxicity caused by cyclophosphamide, melphalan and procarbazine therapy, Tumori Aug 31 1987 73 (4) p351-8 ; CORNWELL, G.G., PAJAK, T.F., McINTIRE, O.R., Hypersensitivity reactions to i.v. melphalan during treatment of multiple myeloma, Cancer Treat. Rep., Mar. 1979; 63 (3): 399-403; LAWRENCE, B.V., Anaphylaxis due to oral melphalan, Cancer Treat. Rep., Apr. - May 1980; 64 (4-5): 731-732.
1.1.4. CYCLOPHOSPHAMIDE.
Chemical denomination: N,N-bis-(ß-chloroethyl) -N'O-propylenephosphoric acid ester-diamide, 2-{bis-(2-chloroethyl)-amino}-tetrahydro-2H-1,3,2-oxazaphoesphorine-2-oxide (NSC 26271).
Action: cyclophospamide is transformed in the body into an active alkylating substance.
Brands: CLAFEN ®, CYTOPHOSPHAN ® (Taro, Haifa), CYTOXAN ® (Mead-Johnson), ENDOXAN ® (Astra), ENDOXANA ® (Ward Blenkinson, Boehringer), PROCYTOX ® (Horner), SENDOXAN ® (Pharmacia), ENDUXAN ® (Brasil), GENOXAL ® (Spain), CYCLOBLASTINE® (Labohain), CYCLOPHOSPHAMIDUM® (INN), CARLOXAN (Farmitalia Denm.), CYCLOBLASTIN® (Austr.), CYCLOSTIN® (Farmit. Germ.), CYCLOSTINE® (Farmit., Carlo Erba Zwits.), NEOSAR® (Adria USA), PROCYTOX® (Canada), SENDOXAN® (Asta Denm., Norw.).
Side effects:
1. Digestive upsets: nausea, anorexie, vomiting, oesofagitis, diarrhoea.
KEARNEY, P.J., Antiemetics for high-dose cyclophosphamide, Br. Med. J., 11 Jan. 1975; 1 (5949): 95-96; BOELEN, H.J., VERHOEVEN, A.T., Een patiènte met ernstige slikklachten na behandeling met cytostatica, Nederl. Tijdschr. Geneesk., 26 Aug. 1978; 122 (34): 1262-1263.
2. Skin affections: and eruptions, hyperpigmention of the skin, nail pigmentation, loss of hair.
N.N., Hyperpigmentation after cancer chemotherapy, Lancet, 19 Jul. 1975; 2 (7925): 128; ROMANKIEWICZ, J.A., Cyclophosphamide and pigmentation, Am. J. Hosp. Pharm., Nov. 1974; 31 (11): 1074-1075; KRUTCHIK, A.N., BUZDAR, A.U., TASHIMA, C.K., Cyclophosphamide-induced urticaria, Arch. Intern. Med., Nov. 1978; 138 (11): 1725-1726; HOLMES, W., Alopecia from chemotherapy: can nursing measures help?, A.N.A. Publ., 1979; (NP-59): 223-233; SULIS, E., FLORIS, C., Nail pigmentation following cancer chemotherapy. A new genetic entity?, Eur. J. Cancer, Nov. 1980; 16 (11): 1517-1519.
3. Impairment of the haematopoiesis: bone marrow depression, anaemia, thrombocytopenia, immunodepression, reversible leucopenia, tendency to bleeding.
VOROBEV, A.I., BRILLIANT, M.D., BARANOV, A.E., Tsitostaticheskaya bolezn voprosu o lekarstvennykh agranulotsitozakh, Ter. Arkh., 1975; 47 (6): 3-11; BURN, J.I., COOKE, W.M., Effect of nadroline phenylpropionate on the bone marrow suppression caused by cyclophosphamide: a clinical trial, Cancer Chemother. Rep., Nov. - Dec. 1974; 58 (6): 867-870; LOHRMANN, H.P., SCHREML, W., HEIMPEL, H., Reaktion der menschlichen Granulopoese auf hochdosierte Cyclophosphamide-Chemotherapie, Verh. Dtsch. Ges. Inn. Med., 1978; (84): 600-604; RINGBORG, U., LEWENSOHN, R., Factors responsible for bone marrow toxicity after treatment of myeloma patients with different alkylating agents, Acta Med. Scand., 1978; 203 (4): 276-278; TZORTZATOU, F., DACOU-VOUTETAKIS, c., HAIDAS, S., PAPADELLIS, F., THOMAIDIS, T., Electrolyte abnormalities in lymphosarcoma after chemotherapy, Acta Pediatr. Scand., Jul. 1979; 68 (4): 621-623.
4. Impairment of the reproductive organs:
BONZALES ZUNIGA, G., AJURIA DE VARGAS, L.M., GORDILLO, G., Alteraciones gonadales en pacientes nefrologicos tratados con ciclofosfamida, Bol. Med. Hosp. Infant. Mex., May - Jun. 1976; 7 (5): 521-523; ETTELDORF, J.N., WEST, C.D., PITCOCK, J.A., WILLIAMS, D.L., Gonodal function, testicular histology and meiosis following cyclophosphamide therapy in patients with nephrotic syndrome, J. Pediatr., Feb. 1976; 88 (2): 206-212; BUCHANAN, J.D., FAIRLEY, K.F., BARRIE, J.U., Return of spermatogenesis after stopping cyclophosphamide therapy, Lancet, 26 Jul. 1975; 2 (7925): 128; PENNISI, A.J., GRUSHKIN, C.M., LIEBERMAN, E., Gonodal function in children with nephrosis treated with cyclophosphamide, Am. J. Dis. Child., Mar. 1975; 129 (3): 315-318; PARRA, A., CERVANTES, C., SOJO, I., CARRANCO, A., CORTES-GALLEGOS, V., Plasma gonadotropins and gonodal steroids in children treated with cyclophosphamide, J. Pediatr., Jan. 1978; 92 (1): 117-124; LENTZ, R.D., BERGSTEIN, J., STEFFES, M.W., BROWN, D.R., PREM, K., MICHAEL, A.F., VERNIER, R.L., Postpubertal evaluation of gonodal function following cyclophosphamide therapy before and during puberty, J. Pediatr., Sep. 1977; 91 (3): 385-394; ALFILER, C.A., Prepubertal cyclophosphamide therapy and gonodal dysfunction: a case report and review of the literature, Austr. Paediatr. J., Jun. 1979; 15 (2): 120-123; FUKUTANI, K., ISHIDA, H., SHINOHARA, M., MINOWADA, S., NIIJIMA, T., HIJIKATA, K., IZAWA, Y., Suppression of spermatogenesis in patients with Behcet's disease treated with cyclophosphamide and colchicine, Fertil. Steril., Jul. 1981; 36 (1): 76-80; TROMPETER, R.S., EVANS, P.R., BARRAT, T.M., Gonadal function in boys with steroid-responsive nephrotic syndrome treated with cyclophosphamide for short periods, Lancet, 30 May 1981; 1 (8231): 1177-1179.
5. Urinary bladder inflamation and bleeding:
JAYALAKSSHMAMMA, B., PINKEL, D., Urinary-bladder toxicity following pelvic irradiation and simultaneous cyclophosphamide therapy, Cancer, Aug. 1976; 38 (2): 701-707; ROYAL, F.E., HOPE, T.O., SEELER, R.A., Adenovirus type II and cyclophosphamide hemorrhagic cystitis, Ill. Med. J., Aug. 1976; 150 (2): 133-135; MAHOUBI, S., DUCKETT, J.N., SPACKMAN, T.J., Uretritis cystica after treatment of cyclophosphamide-induced hemorrhagic cystitis, Urology, May 1976; 7 (5): 521-523; LAWRENCE, H.J., SIMONE, J., AUR, R.J., Cyclophosphamide-induced hemorrhagic cystitis in children with leukemia, Cancer, Nov. 1975; 36 (5): 1572-1576; SUGIURA, H., KATO, J., Cyclophosphamide hemorrhagic cystitis, Jpn. J. Urol., Dec. 1974; 65 (12): 816-821; SCETBON, V., Hématurie incoercible par traitement prolongé par cyclophosphamide, J. Urol. Nephrol. (Paris), Dec. 1973; 79 (12 Pt. 2): 472-476; FRANCIS, R.S., SHACKLEFORD, G.D., Cyclophosphamide cystitis with bladder wall calcification, J. Can. Assoc. Radiol., Dec. 1974; 25 (4): 324-326; BORRELLI, M., SROUGI, M., DE GOES, G.M., CAMPOS-FREIRE, J.G., Cistite hemorragica pela ciclofosfamida, Rev. Paul. Med., Jul. 1973; 82 (1): 17-24; PYERITZ, R.E., DROLLER, M.J., BENDER, W.L., SARAL, R., An approach to the control of massive hemorrhage in cyclophosphamide-induced cystitis by intravenous vasopressin: a case report, J. Urol., Aug. 1978; 120 (2): 253-254; WELLER, R.E., Intravesical instillation of dilute formalin for treatment of cyclophosphamide-induced hemorrhagic cystitis in two dogs, J. Am. Vet. Med. Assoc., 15 May 1978; 172 (10): 1206-1209; BRÜHL, P., HOEFFER-JANKER, H., SCHEEF, W., VAHLENSIECK, W., Prophylaktische Alkalisierung des Harns bei zytostatischer Tumorbehandlung mit Oxazaphosphorin-Derivaten Cyclophosphamide und Ifosfamid, Onkologie, Jun. 1979; 2 (3): 120-124; MARSHALL, F.F., KLINEFELTER, H.F., Late hemorrhagic cystitis following low-dosis cyclophosphamide therpay, Urology, Dec. 1979; 14 (6): 573-575; HARLOW, P.J., DECLERCK, Y.A., SHORE, N.A., ORTEGA, J.A., CARRANZA, A., HEUSER, E., A fatal case of inappropriate ADH secretion induced by cyclophosphamide therpay, Cancer, Sep. 1979; 44 (3): 896-898; TEXTER, J.H.Jr., McWILLIAMS, N.B., Hemorrhagic cystitis as a complication of the management of pediatric neoplasms, Urol. Surv., Apr. 1979; 29 (2): 47-48; PLOTZ, P.H., KLIPPEL, J.H., DECKER, J.L., GRAUMAN, D., WOLFF, B., BROWN, B.C., RUTT, G., Bladder complications in patients receiving cyclophosphamide for systemic lupus erythematosus or rheumatoid arthritis, Ann. Intern. Med., Aug. 1979; 91 (2): 221-223; RABINOVITCH, H.H., Simple innocous treatment of massive cyclophosphamide hemorrhagic cystitis, Urology, Jun. 1979; 13 (6): 610-612.
6. Pulmonary disease:
PATEL, A.R., SHAH, P.C., RHEE, H.L., SASSOON, H., RAD, K.P., Cyclophosphamide therapy and interstitial pulmonary fibrosis, Cancer, Oct. 1976; 38 (4): 1542-1549; WILLSON, J.K., Pulmonary toxicity of antineoplastic drugs, Cancer Treat. Rep., Dec. 1978; 62 (12): 2003-2008; MARK, G.J., LEHIMGAR-ZADEH, A., RAGSDALE, B.D., Cyclophosphamide pneumonitis, Thorax, Feb. 1978; 33 (1): 89-93; ALVARADO, C.S., BOAT, T.F., NEWMAN, A.J., Late-onset pulmonary fibrosis and chest deformity in two children treated with cyclophosphamide, J. Pediatr., Mar. 1978; 92 (3): 443-446; SPECTOR, J.I., ZIMBLER, H., ROSS, J.S., Early-onset cyclophosphamide-induced interstitial pneumonitis, J.A.M.A., 28 Dec. 1979; 242 (26): 2852-2854; MÜLLER, K.M., MENNE, R., HÜTHER, W., GRÜBE, H., Fatal pneumopathy after cytostatic treatment for leukemia in children, J. Cancer Res. Clin. Oncol., 27 Jul. 1979; 94 (3): 287-294; BRANDMAN, J.R., RUCKDESCHEL, J.C., O'DONNELL, M.R., HORTON, J.,Small cell cancer of lung: rapid tumor necrosis leading to serious pulmonary infections after intensive chemotherpay, N.Y. State J. Med., Aug., 1981; 81 (9): 1332-1334; PLANK, L., BUCHANEC, J., Pulmonary comlications of cytostatic treatment of hemoblastosis (Slovakian), Cesk. Pediatr., Mar. 1980; 35 (3): 164-166; SPECTOR, J.I., ZIMBLER, H., ROSS, J.S., Cyclophosphamide and interstital pneumonitis, J.A.M.A., 21 Mar. 1980; 243 (11): 1133.
7. Mutagenic effects:
SCHAISON, G., JACQUILLAT, C., AUCLERC, G., WEIL, M., Les risques foeto-embryonnaires des chimiothérapies, Bull. Cancer (Paris), 1979; 165-170; STROZYNSKI, H., BODALSKI, J., NAREBSKA, E., Chromosome aberrations in children with glomerulonephritis treated with cyclophosphamide (Polish), Pol. Tyg. Lek., 8 Dec. 1980; 35 (49): 1893-1895.
8. Cancer-producing:
WEST, W.O., Acute erythroid leukemia after cyclophosphamide therapy for multiple myeloma, South Medical J., Oct. 1976; 69 (10): 1331-1332; LOVE, R.R., SOWA, J.M., Myelomonocytic leukemia following cyclophosphamide therapy of rheumatoid disease, Ann. Rheum. Dis., Dec. 1975; 34 (6): 534-535; GUTJAHR, P., SPRANGER, J., Acute leukemia following anticancer treatment, J. Pediatr., Dec. 1975; 87 (6 Pt. 1): 1004-1005; ANSELL, I.D., CASTRO, J.E., Carcinoma of the bladder complicating cyclophosphamide therapy, Br. J. Urol., Aug. 1975; 47 (4): 413-418; WEINSTEIN, S.H., MILLEMAN, L.A., SCHMIDT, J.D., Cyclophosphamide, J. Urol., Jul. 1975; 114 (1): 157; DALE, G.A., SMITH, R.B., Transitional cell carcinoma of the bladder associated with cyclophosphamide, J. Urol., Nov. 1974; 112 (5): 603-604; PARISER, S., Myeloblastic leukemia following immunosuppressive therapy for rheumatoid arthritis, Am. J. Clin. Pathol., Aug. 1978; 70 (2): 301-302; PEARSON, R.M., SOLOWAY, M.S., Does cyclophosphamide induce bladder cancer?, Urology, May 1978; 11 (5): 437-447; SETZER, S.E., BENAZZI, R.B., KEARNEY, G.P., Cyclophosphamide and carcinoma of the bladder, Urology, Apr. 1978; 11 (4): 352-356; HOCHBERG, M.C., SHULMAN, L.E., Acute leukemia following cyclophosphamide therapy for Sjörgen's syndrome, John Hopkins Med. J., Jun. 1978; 142 (6); 211-214; MOUGEOT-MARTIN, M., KRULIK, M., HAROUSSEAU, J.L., AUDEBERT, A.A., CHAOUAT, Y., DEBRAY, J., Leucémies aigues survenues au décours d'une maladie de Behcet et d'une sclérose en plaques traitées par immunosuppresseurs, Ann. Méd. Interne (Paris), Mar. 1978; 129 (3): 175-180; LENZIN, A., CAVALLI, F., SONNTAG, R., ZIMMERMANN, A., Blasenkarzinom bei langjähriger Behandlung mit Cyclophosphamid wegen multiplem Myelom, Urologe (Austr.), Mar. 1978; 17 (2): 105-108; ELLIOTT, G.B., SILVERBERG, D.S., DOSSETOR, J.B., MUIR, C.S., Latent carcinoma of the prostrate in a 24-year-old man receiving cyclophosphamide and azathioprine, Can. Med. Assoc. J., 19 Mar. 1977; 116 (6): 651-652; MARKS, J.S., SCHOLTZ, C.L., Sarcoma complicating therapy with cyclophosphamide, Postgrad. Med. J., Jan. 1977; 53 (615): 48-49; PURI, H.C., CAMPBELL, R.A., Cyclophosphamide and malignancy, Lancet, 18 Jun. 1977; 1 (8025): 1306; CHANG, J., GEARY, C.G., Therapy-linked leukemia, Lancet, 8 Jan. 1977; 1 (8002): 97; DE RUITER, J., CRAMER, S.J., SMINK, T., VAN PUTTEN, L.M., The facilitation of tumor growth in the lung by cyclophosphamide in artificial and spontaneous metastases models, Eur. J. Cancer, Sep. 1979; 15 (9): 1139-1145; KAHN, M.F., ARLET, J., BLOCH-MICHEL, H., CAROIT, M., CHAOUAT, Y., RENIER, J.C., Leucémies aigues après traitement par agents cytotoxiques en rhumatologie. 19 observations chez 2006 patients, Nouv. Presse Méd., 14 Apr. 1979; 8 (17): 1393-1397; SHINOZAKI, Y., ITO, M., Acase of myeoblastic leukemia after immunosuppressive therapy for nephrosis (Japanese), Rinso Ketsweki, Jun. 1979; 20 (6): 651-657; ALTHOUSE, R., HUFF, J.E., TOMATIS, L., WILBOURN, J.D., Cyclophosphamide in chronic active hepatitis, Br. Med. J., 16 Jun. 1979; 1 (6178): 1630-1631; FAIRCHILD, W.V., SPENCE, C.R., SOLOMON, H.D., GANGAI, M.P., The incidence of bladder cancer after cyclophosphamide therapy, J. Urol., Aug. 1979; 122 (2): 163-164; GARVIN, D.D., BALL, T.P.Jr., Bladder malignancy in patient receiving cyclophosphamide for benign disease, Urology, Jul. 1981; 18 (1): 80-81; KRAUSE, J.R., Acute nonlymphocyte leukemia after cyclophosphamide therapy for refractory idiopathic thrombocytopenic purpura, South. Med. J., Jul. 1981; 74 (7): 891-892; McDOUGAL, W.S., CRAMER, S.F., MILLER, R., Invasive carcinoma of the renal pelvis following cyclophosphamide therapy for nonmalignant disease, Cancer, 1 Aug. 1981; 48 (3): 691-695; ADIGA, K.M., Bladder tumour after treatment in lymphoma, Med. J. Aust., 21 Feb. 1981; 1 (4): 190; WHEELER, G.E., Cyclophosphamide-associated leukemia in Wegener's granulomatosis, Ann. Intern. Med., Mar. 1981; 94 (3): 361-362; DURKEE, C., BENSON, R. Jr., Bladder cancer following administration of cyclophosphamide, Urology, Aug. 1980; 16 (2): 145-148; CHASKO, C.B., KEUHNELIAN, J.G., GUTOWSKI, W.T., 3d., GRAY, G.F., Spindle cell cancer of bladder during cyclophosphamide therapy for Wegener's granulomatosis, Am. J. Surg. Pathol., Apr. 1980; 4 (2): 191-196.
9. Cardiotoxicity:
GOTTDIENER, J.S., APPELBAUM, F.R., FERRANS, V.J., DEISSEROTH, A., ZIEGLER, J., Cardioxicity associated with high-dose cyclophosphamide therapy, Arch. Intern. Med., May 1981; 141 (6): 758-763; VON BERNUTH, G., ADAM, D., HOFSTETTER, R., LANG, D., MOHR, W., KOHNE, E., NIETHAMMER, D., Cyclophosphamide cardioxicity, Eur. J. Pediatr., Jun. 1980; 134 (1): 87-90.
10. Miscellanea:
Lupera H; Droz JP; Culine S; Perrin JL; Court BH; Ghosn M; Hayat M, Cancer of the bladder after treatment with cyclophosphamide. Apropos of a case and a review of the literature, J Urol (Paris) (FRANCE) 1990 96 (1) p48-52; Carneiro PC; Pereira ED; Mitteldorf CS; Martinez GA; Beitler B; Pozzi DH , Acute myeloid leukemia after treatment of Hodgkin's disease, Rev Hosp Clin Fac Med Sao Paulo (BRAZIL) Mar-Apr 1989 44 (2) p87-90; Webberley MJ; Murray JA , Life-threatening acute hyponatraemia induced by low dose cyclophosphamide and indomethacin, Postgrad Med J (ENGLAND) Dec 1989 65 (770) p950-2; Thrasher JB; Miller GJ; Wettlaufer JN , Bladder leiomyosarcoma following cyclophosphamide therapy for lupus nephritis, J Urol (UNITED STATES) Jan 1990 143 (1) p119-21; Hoffman GS; Leavitt RY; Fauci AS , Infectious complications of cyclophosphamide treatment for vasculitis [letter], Arthritis Rheum (UNITED STATES) Dec 1989 32 (12) p1626-7 ; Dore B; Grange P; Aubert J , Cancer of the bladder after cystitis due to cyclophosphamide. Apropos of a case, J Urol (Paris) (FRANCE) 1989 95 (7) p427-31; Escalante A; Kaufman RL; Beardmore TD, Acute myelocytic leukemia after the use of cyclophosphamide in the treatment of polyarteritis nodosa, J Rheumatol (CANADA) Aug 1989 16 (8) p1147-9; Beelen DW; Quabeck K; Graeven U; Sayer HG; Mahmoud HK; Schaefer UW , Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia, Blood (UNITED STATES) Oct 1989 74 (5) p1507-16; Kudriavskaia VM; Pyrit LA; Rudenko AV , Complications caused by fungi of the genus Candida in patients with glomerulonephritis during pathogenetic therapy, Vrach Delo Jun 1988 (6) p82-5 ; LeBaron S; Zeltzer LK; LeBaron C; Scott SE; Zeltzer PM , Chemotherapy side effects in pediatric oncology patients: drugs, age, and sex as risk factors, Med Pediatr Oncol 1988 16 (4) p263-8 ; Ushiki N; Jobo T; Shimoda T; Kuramoto H; Arai M , Effects of cepharanthin on leukopenia and thrombocytopenia caused by CDDP- ACR-CPA therapy of ovarian cancer, Gan To Kagaku Ryoho Sep 1988 15 (9) p2701-6; Slease RB; Benear JB; Selby GB; Reitz CL; Hughes WL; Watkins CL; Epstein RB , High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors, J Clin Oncol Aug 1988 6 (8) p1314-20 ; Manzione NC; Wolkoff AW; Sassa S , Development of porphyria cutanea tarda after treatment with cyclophosphamide, Gastroenterology (UNITED STATES) Oct 1988 95 (4) p1119-22 ; Kirshon B; Wasserstrum N; Willis R; Herman GE; McCabe ER , Teratogenic effects of first-trimester cyclophosphamide therapy, Obstet Gynecol (UNITED STATES) Sep 1988 72 (3 Pt 2) p462-4 ; Laing EJ; Miller CW; Cochrane SM , Treatment of cyclophosphamide-induced hemorrhagic cystitis in five dogs, J Am Vet Med Assoc (UNITED STATES) Jul 15 1988 193 (2) p233-6; Chu DT; Wong WL; Mavligit GM , Immunotherapy with Chinese medicinal herbs. II. Reversal of cyclophosphamide-induced immune suppression by administration of fractionated Astragalus membranaceus in vivo, J Clin Lab Immunol Mar 1988 25 (3) p125-9; Carter JL; Hafler DA; Dawson DM; Orav J; Weiner HL , Immunosuppression with high-dose i.v. cyclophosphamide and ACTH in progressive multiple sclerosis: cumulative 6-year experience in 164 patients, Neurology Jul 1988 38 (7 Suppl 2) p9-14 ; Mulder PO; de Vries EG; Koops HS; Splinter T; Maas A; van der Geest S; Mulder NH; Sleijfer DT , Chemotherapy with maximally tolerable doses of VP 16-213 and cyclophosphamide followed by autologous bone marrow transplantation for the treatment of relapsed or refractory germ cell tumors, Eur J Cancer Clin Oncol Apr 1988 24 (4) p675-9 ; Allan SG; Cheyne AJ; Warrington PS; Cornbleet MA , Emesis and cancer chemotherapy [letter], Eur J Cancer Clin Oncol Mar 1988 24 (3) p503; Palmer RG; Smith-Burchnell CA; Pelton BK; Hylton W; Denman AM , Use of T cell cloning to detect in vivo mutations induced by cyclophosphamide, Arthritis Rheum (UNITED STATES) Jun 1988 31 (6) p757-61; Glatt E; Henke M; Sigmund G; Costabel U, Cyclophosphamid-induzierte Pneumonitis, ROFO (GERMANY, WEST) May 1988 148 (5) p545-9 ; Jerkins GR; Noe HN; Hill D, Treatment of complications of cyclophosphamide cystitis, J Urol (UNITED STATES) May 1988 139 (5) p923-5 ; Rao SV; Murugesan K; Vij U; Sarin R; Kapur BM , Effect of cancer polychemotherapy on gonadal function in Hodgkin's disease in adult men, Indian J Med Res Jan 1988 87 p37-41 ; Stillwell TJ; Benson RC Jr; DeRemee RA; McDonald TJ; Weiland LH, Cyclophosphamide-induced bladder toxicity in Wegener's granulomatosis, Arthritis Rheum Apr 1988 31 (4) p465-70 ; Patakfalvi A; Gelencser E; Sipos J , Drug hepatitis of cholestatic type in association with a FAC-regimen for breast cancer, Acta Med Hung 1987 44 (4) p377-85 ; Pedersen-Bjergaard J; Ersboll J; Hansen VL; Sorensen BL; Christoffersen K; Hou-Jensen K; Nissen NI; Knudsen JB; Hansen MM , Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma, N Engl J Med Apr 21 1988 318 (16) p1028-32 ; Rossi GA; Balbi B; Benatti U; Morelli A; Sacco O; Vassallo F; Ravazzoni C, Changes in pulmonary surfactant composition following MACC chemotherapy for lung carcinoma, Eur J Respir Dis Nov 1987 71 (5) p400-9; Sagawa M; Takahashi S; Usuda K; Kamma K; Satoh M; Ohta S; Nagamoto N; Imai T; Saitoh Y; Suda H; et al , Interstitial pneumonia after CMC (CDDP, MMC, CPM) therapy, Gan No Rinsho Feb 1988 34 (2) p150-4 ; Rivkees SA; Crawford JD , The relationship of gonadal activity and chemotherapy-induced gonadal damage, JAMA Apr 8 1988 259 (14) p2123-5 ; Stillwell TJ; Benson RC Jr , Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients, Cancer Feb 1 1988 61 (3) p451-7 ; Saito T; Ikeda Y; Ito E; Miyano K; Kawauchi K; Yokoyama M; Sato Y , Bladder irrigation with prostaglandin E2 in cyclophosphamide-induced hemorrhagic cystitis, Gan To Kagaku Ryoho Jan 1988 15 (1) p155-7 ; Parker R, The effectiveness of scalp hypothermia in preventing cyclophosphamide- induced alopecia, Oncol Nurs Forum Nov-Dec 1987 14 (6) p49-53; Kalinicheva EO; Papaian AV, Effect of cytostatic preparations used in the treatment of glomerulonephritis in children on the functional activity of the gonads, Pediatriia (USSR) 1987 (10) p102-4 ; Hernadi Z; Juhasz B; Poka R; Mahunka I; Lampe L , Analysis of the effectiveness and adverse effects of the drug combinations CAP and CEP in the therapy of patients in the advanced stages of ovarian cancer, Orv Hetil Nov 22 1987 128 (47) p2457-61 ; Stillwell TJ; Benson RC Jr; Burgert EO Jr , Cyclophosphamide-induced hemorrhagic cystitis in Ewing's sarcoma, J Clin Oncol Jan 1988 6 (1) p76-82 ; Linssen WH; Notermans NC; Hommes OR; Rolland R , Amenorrhea after immunosuppressive treatment of multiple sclerosis, Acta Neurol Scand (DENMARK) Sep 1987 76 (3) p204-9 ; Kanoh T , Gross hematuria in multiple myeloma, Nippon Ketsueki Gakkai Zasshi (JAPAN) Jul 1987 50 (4) p911-3 ; Sauer H; Kremer G; Wilmanns W , Zur Toxizitat einer CYVADIC-Modifikation bei Patienten mit Weichteilsarkomen oder malignen Mesotheliomen, Onkologie Oct 1987 10 (5) p294-300 ; Humblet Y; Symann M; Bosly A; Delaunois L; Francis C; Machiels J; Beauduin M; Doyen C; Weynants P; Longueville J; et al , Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study,
J Clin Oncol Dec 1987 5 (12) p1864-73 ; Sargent LM; Roloff B; Meisner LF , Mechanisms in cyclophosphamide induction of cytogenetic damage in human lymphocyte cultures, Cancer Genet Cytogenet (UNITED STATES) Dec 1987 29 (2) p239-43; Berger J , Age-related sensitivity of rats to induction of anaemia, Folia Haematol (Leipz) (GERMANY, EAST) 1987 114 (3) p408-13 ; Hawkins MM; Draper GJ; Kingston JE, Incidence of second primary tumours among childhood cancer survivors, Br J Cancer Sep 1987 56 (3) p339-47 ; Lauta VM; Valerio G; Greco A; Capece Minutolo M , Early-onset diagnosis of lung toxicity caused by cyclophosphamide, melphalan and procarbazine therapy, Tumori Aug 31 1987 73 (4) p351-8 DISVETOVA, V.V., LEVITIN, E.I., TRAKHTENBERG, A. Kh., BATINOV, I.N., Kinetischeskie zakonomernosti izmeneiia chisl leikotsitov v perofericheskoi krovi bol'nykh rakom legkogo pri lechenii tsikofosfanom v sochetanii s tsistafosfom; Izv. Akad. Nauk. SSSR (Biol.), May - Jun. 1977; (3): 351-356; GADGIL, S.D., SHETTY, P.A., MEHTA, A.R., NADKARNI, K.S., JUSSAWALLA, D.J., Study of dose-related cyclophosphamide toxicity in patients of head and neck cancers, Indian J. Cancer, Mar. 1980, 17 (1): 51-54.
1.1.5. PREDNIMUSTINE
Chemical denomination: 11ß,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-(4-{4-[bis(2-chloorethyl)-amino]-fenyl}butyraat). (NSC 134087).
Action: like chlorambucil.
Brands: MOSTARINE® (Abello), STEREOCYT® (Bellon), STERECYT® (Pharmacia Arzneimittel, Leo).
Methanesulfonates:
1.2.1. BUSULPHAN
Only BUSULPHAN is used for therapeutic purposes.
Chemical denomination: 1,4-(dimethylsulfonyl) 1,4 dioxy-butane. (NSC 750).
Action: is a bone marrow selective alkylating substance.
Brands: MYELUCIN ® (Simes), MISULBAN ® (Techni Pharma, Monaco), MITOSTAN ®, MYELEUKON ® (Arzneimittelwerk Dresden, D.D.R.), MYLERAN ® (Burroughs Wellcome), SULFABUTIN ®, MYELOSAN ® (U.S.S.R.), BUSULFANUM® (INN).
Side effects:
1. Digestive upsets: vomiting, nausea (rarely)
2. Skin affections: hyperpigmentation of the skin, als a part of a pseudo-Addison syndrome, retina affections.
HAMMING, N.A., APPLE, D.J., GOLDBERG, M.F., Histopathology and ultrastructure of busulfan-induced cataract, Albrecht Von Graefes Arch. Klin. Ophtalmol., 30 Aug. 1976; 200 (2): 139-147; LEYDEN, M.J., MANOHARAN, A., "Aloopurinol-type"-rash due to busulfan, Lancet, 7 Oct. 1978; 2 (8093): 797; SARAUX, H., LEFRANCOIS, A., Degenerative Netzhauterkrankungen nach Behandlung der Mutter mit Busulfan während der Schwangershaft, Klin. Monatsbl. Augenheilk., Jun. 1977; 170 (6): 818-820.
3. Impairment of the haematopoiesis: bone marrow depression, blood composition alteration.
PEZZIMENTI, J.F., KIM, H.C., LINDENBAUM, J., Erythroleukemia-like syndrome due to Busulfan toxicity in polycythemia vera, Cancer, Dec. 1976; 38 (6): 2242-2246; STUART, J.J., CROCKER, D.L., ROBERTS, H.R., Treatment of busulfan-induced pancytopenia, Arch. intern. Med., Oct. 1976; 136 (10): 1181-1183; HAST, R., Increase in serum alkaline phosphatase in chronic myelocytic leukemia, sign of drug-induced choletasis?, Acta Med. Scand., 1978; 203 (1-2): 93-94; DEMIDOVA, A.V., POGORZHELSKI, V.I., Case of Myelosan-induced hemapoietic aplasia in erythremia (Russian), Ter. Arkh., 1977; 49 (2): 133-134; WOHL, M.A., WOOD, J.K., Chronic myeloid leukemia and a myasthenic syndrome, Acta Haematol. (Basel), 1979; 62 (4): 214-218.
4. Inflamation and bleeding of the bladder:
MILLARD, R.J., Busulfan hemorrhagic cystitis, Br. J. Urol., May 1978; 50 (3): 210.
5. Pulmonary disease: the so-called BUSULPHAN-lung (pulmonary fibrosis)
KOCH, H., LESCH, R., Busulfanlunge. Lungenfibrose durch Myleran, Med. Welt, 13 Feb. 1976; 27 (7): 308-311; JANDL, H., FRANKE, A., ALBRECHT, G., Lungenfibrose nach Busulfantherapie, Z. Gesamte Inn. Med., 15 Dec. 1975; 30 (24): 799-801; SAWADA, S., TAKAHIRA, Y., OKAMOTO, K., KOBAYASHI, A., MATSUDA, M., NAKAZAWA, M., Busulfan-lung (Japanese), Rinsho Hoshasen, Oct. 1978; 23 (10): 1047-1051; HANKINS, D.G., SANDERS, S., MacDONALD, F.M., DRAGE, C.W., Pulmonary toxicity recurring after a six week course of busulfan therapy and after subsequent therapy with uracil mustard, Chest, Mar. 1978; 73 (3): 415-416; MIYASHITA, T., OJIMA, A., TUJI, T., TAJIMA, T., WATANABE, K., Varied pulmonary lesions with intraalveolar large lamellar bodies in an autopsy case with busulfan therapy, Acta Pathol. (Japan), Mar. 1977; 27 (2): 239-249; DOUAY, B., LEDUC, M., BEAUGEARD, D., Une observation de poumon au misulban, Lille Méd., Apr. 1979; 24 (4): 292-294; DAKHILL, A., GREEN, I.D., KNOWLSON, G.T. CAMERON, A.H., SHAH, K.J., HILL., F.G., MANN, J.R., Busulfan lung in childhood, J. Clin. Pathol., May 1981; 34 (5): 495-500; DALRI, P., PISCIOLI, F., DETASSIS, C., Busulfan-lung: cytologic diagnosis, Haematologica (Pavia), Aug. 1980; 65 (4): 469-474; MANNING, D.M., STRIMLAN, C.V., TURBINER, E.H., Early detection of busulfan lung: report of a case, Clin. Nucl. Med., Sep. 1980; 5 (9): 412-414.
6. Mutagenic side effects:
KRAJINCANIC, B., LAZAROV, A., ZUNIC, Z., RADOJICIC, B., Chromosome changes in patients treated with "Myleran", Strahlentherapie, May 1976; 151 (5): 459-462; ABRAMOVICI, A., SHAKLAI, M., PINKHAS, J., Myeloschisis in a six weeks embryo of a leukemic woman treated bu busulfan, Teratology, Oct. 1978; 18 (2): 241-246.
7. Impairment of the reproductive organs: sterility, azoospermia, amenorrhea, impotence, gynecomastia.
8. Carcinogenic effects: may cause leukemia.
STOTT, H., FOX, W., GIRLING, D.J., STEPHENS, R.J., GALTON, D.A., Acute leukemia after busulfan, Br. Med. J., 10 Dec. 1977; 2 (6101): 1513-1517.
9. Miscellanea:
Watanabe K; Sueishi K; Tanaka K; Nagata N; Hirose N; Shigematsu N; Miake S; Yoshida M , Pulmonary alveolar proteinosis and disseminated atypical mycobacteriosis in a patient with busulfan lung, Acta Pathol Jpn (JAPAN) Jan 1990 40 (1) p63-6; Zuazu I; Brunet S; Fernandez MT; Domingo-Albos A , Hepatic veno-occlusive disease in a patient undergoing bone marrow autotransplant after busulfan and melphalan conditioning (letter), Med Clin (Barc) (SPAIN) Jan 27 1990 94 (3) p119; Kaldor JM; Day NE; Pettersson F; Clarke EA; Pedersen D; Mehnert W; Bell J; Host H; Prior P; Karjalainen S; et al , Leukemia following chemotherapy for ovarian cancer, N Engl J Med (UNITED STATES) Jan 4 1990 322 (1) p1-6. Note: Comment in: N Engl J Med 1990 Jan 4;322(1):52-3; Van Linthoudt D; Ott H , Does osteoporosis related to cytostatic drugs exist?, Med Hypotheses (ENGLAND) Aug 1989 29 (4) p293-4 ; Peters WG , Liver damage during use of busulfan (letter), Ned Tijdschr Geneeskd (NETHERLANDS) Sep 16 1989 133 (37) p1849-50; Adang RP; Breed WP , Liver damage during use of busulfan, Ned Tijdschr Geneeskd (NETHERLANDS) Jul 29 1989 133 (30) p1515-8 ; Beelen DW; Quabeck K; Graeven U; Sayer HG; Mahmoud HK; Schaefer UW , Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia, Blood (UNITED STATES) Oct 1989 74 (5) p1507-16; WEINBERGER, A., PINKHAS, J., SANDBANK, U., SHAKLAI, M., DE VRIES, A., Endocardial fibrosis following busulfan treatment, J.A.M.A., 3 Feb. 1975; 231 (5): 495; JAPP, H., Toxische Effekte von Busulfan (Myleran) bei der Behandlung der chronischen myeloischen Leukämie, Schweiz. Med. Wochenschr., 10 Aug. 1974; 104 (32): 1115-1119; JAPP, H., Unerwünschte Nebenwirkungen von Busulfan, Dtsch. Med. Wochenschr., 20 Dec. 1974; 99 (51): 2614-2615; ZAWADA, W., Two cases of primary erythremia treated with busulfan, Mater. Med. Pol., Apr. - Jun. 1974; 6 (2): 140-142; SIDI, Y., DOUER, D., PINKHAS, J., Sicca syndrome in a patient with toxic reaction to busulfan, J.A.M.A., 31 Oct. 1977; 238 (18): 1951; MORALES-POLANCO, M.R., BUTRON, L., ECHEGOYEN, G., PIZZUTO CHAVEZ, J., Sialoadenitis cronica. Menifestacion toxica del empleo prolonga de busulfan en el tratamiento de la leucemia granulocitica cronica Sangre (Barcelona), 1977; 22 (2): 243-251; ROLFE, M., Splenectomy and chronic myeloid leukemia, Med. J. Zambia, Oct. 1980; 14 (6): 118; Minnella AM; Yannuzzi LA; Slakter JS; Rodriquez A, Bilateral perifoveal ischemia associated with chronic granulocytic leukemia. Case report, Arch Ophthalmol Sep 1988 106 (9) p1170-1; Fernandez LA; Zayed E , Busulfan-induced sideroblastic anemia, Am J Hematol Jul 1988 28 (3) p199-200 ; Hiraoka A; Masaoka T; Shibata H; Miyazaki T; Nakamura T; Yasunaga K; Kitani T; Yonezawa T; Kawagoe H; Horiuchi A; et al, A new nitrosourea derivative for the treatment of chronic myelogenous leukemia, Japan. Leuk Res 1988 12 (6) p487-90 ; Pawelec G; Schmidt H; Schneider E; Buhring HJ; Ehninger G , Cellular immunological defects of chronic myelogenous leukaemics: partial dependence on busulphan therapy, Cancer Immunol Immunother 1988 27 (1) p89-94 ; Morris LE; Guthrie TH Jr, Busulfan-induced hepatitis, Am J Gastroenterol (UNITED STATES) Jun 1988 83 (6) p682-3; Sparaventi G; Manna A; Muretto P; Pazzaglia C; Palazzi M, Malignant melanoma of the glans penis in a chronic myeloid leukemia patient after busulfan therapy, Tumori Dec 31 1987 73 (6) p 645-8; Furuse N; Hayasaka S; Yamamoto Y; Setogawa T, Retinal microaneurysms in a patient with drug-induced aplastic anemia, Ophthalmologica (SWITZERLAND) 1987 195 (4) p188-91; Shalev O; Rahav G; Milwidsky A, Reversible busulfan-induced ovarian failure, Eur J Obstet Gynecol Reprod Biol Nov 1987 26 (3) p239-42 ; Key NS; Kelly PM; Emerson PM; Chapman RW; Allan NC, Oesophageal varices associated with busulphan-thioguanine combination therapy for chronic myeloid leukaemia, Lancet Nov 7 1987 2 (8567) p1050-2 ;
1.3. Ethylenimine-group.
1.3.1. TRIETHYLENEMELAMINE
Chemical denomination: 2,4,6, triethylenimino-1,3,5 triazine (NSC 9706)
Action: as an alkylating agent.
Brands: T.E.M. ® (Hoechst, Lederle, Simes), TRIAMELINE ® (I.C.I.).
Side effects:
1. Digestive upsets: vomiting, nausea, diarrhoea
2. Bone marrow depression.
3. Renal and liver damage.
4. Ologospermia.
Generoso WM; Rutledge JC; Cain KT; Hughes LA; Downing DJ , Mutagen-induced fetal anomalies and death following treatment of females within hours after mating, Mutat Res (NETHERLANDS) May 1988 199 (1) p175-81; Morris SM; Kodell RL; Domon OE; Bishop JB , Detection of TEM-induced reciprocal translocations in F1 sons of CD-1 male mice: comparison of sequential fertility evaluation and cytogenetic analysis, Environ Mol Mutagen 1988 11 (2) p215-23;
1.3.2. TRIETHYLENE(THIO)-
PHOSPHORAMIDE.Chemical denomination: triethyleen(thio)fosforamide; tris(1-aziridinyl)-fosfinesulfide. (NSC 6396).
Action: (probably) by alkylating of nucleic acid of chromosomes of proliferating cells.
Brands: LEDERTEPA ® (Lederle), ONCOTIOTEPA ® (Simes, Brussel), THIO-TEPA S ® (Lederle), THIFOSYL ® (Astra), THIOTEPA ® (Specia), THIOTEPUM ® (INN).
Side effects:
1. Digestive upsets: nausea, anorexia, vomiting
2. Skin affections:
HORNBLASS, A., ADLER, R.I., VUKCEVICH, W.M., GOMBOS, G.M., A delayed side-effect of topical thiotepa, Ann. Ophtalmol., Nov. 1974; 6 (11): 1155-1157; GREENSPAN, E.M., JAFFREY, I., BRUCKNER, H., Thiotepa, cutaneous reactions and efficacy, J.A.M.A., 23 May 1977; 237 (21): 2288.
3. Important impairment of the hematopoietic system: lymfopenia, neutro-, thrombo-, erythrocytes depression, bone marrow depression, irreversible hypoplasic anemia, bleeding.
NAVAS, P., GRASSET, D., Aplasies médullaire mortelle par thiotépa endovésical, J. Urol. Nephrol. (Paris), Dec. 1973; 79 (12 Pt. 2): 489-491; SHUVAEVA, N.I., EMILIANOVA, L.S., Toxic reactions during treatment of the ovarian cancer with thiotepa (Russian), Akush. Ginekol. (Moscou), Oct. 1974; (10): 18-20; VORONKO, E.A., FRADKIN, S.Z., Blood changes in hyperthermic perfusion with chemotherapeutic preparations (Russian), Vopr. Onkol., 1974; 20 (1): 98; RAMPAL, M., ALIMI, J.C., PONS, G., FIQUET, J.M., La nocivité des instillations endo-vésicales de thiotepa en cas de reflux vésico-rénal, J. Urol. Nephrol. (Paris); Mar. 1978; 84 (3): 271-274; BLANK, M.A., Cytogenic analysis of the damaging effect of thiophosphamide on the bone-marrow of patients with malignant tumors (Russian), Vopr. Onkol., 1979; 25 (10): 72-73; MALLING, N., Depression of bone marrow after intravesical use of thiotepa (Danish), Ugeskr. Laeger., 29 Sep. 1980; 142 (40): 2630-2631; HOLLISTER, D. Jr., COLEMAN, M., Hematologic effects of intravesicular thiotepa therapy for bladder carcinoma, J.A.M.A., 7 Nov. 1980; 244 (18): 2065-2067.
4. Bladder affections:
MAYOR, G., Les lésions vésicales par administration locale ou par ingestion de produits antiseptiques, cytostatiques et radioactifs, J. Urol. Nephrol. (Paris), Dec. 1973; 79 (12 Pt. 2): 483-484.
5. Cancer-producing effect:
GREENSPAN, E.M., TUNG, B.G., Acute myeoblastic leukemia after cure of ovarian cancer, J.A.M.A., 21 Oct. 1974; 230 (3): 418-420; KAPADIA, S.B., KRAUS, J.R., Ovarian carcinoma terminating in acute non-lymphocytic leukemia following alkylating agent therapy, Cancer, May 1978; 41 (5): 1676-1679; CHAN, P.Y., SADOFF, L., WINKLEY, J.H., Second malignancies following first breast cancer in prolonges thiotepa adjuvant chemotherapy, in SALMON, S.E., JONES, S.E. (Eds.), Adjuvant therapy of cancer, Amsterdam, North-Holland Publ., 1977; pp. 597-607; SHEIBANI, K., BUKOWSKI, R.M., TUBBS, R.R., SAVAGE, R.A., SEBEK, B.A., HOFFMAN, G.C., Acute non-lymphocytic leukemia in patients receiving chemotherapy for nonmalignant diseases, Hum. Pathol., Mar. 1980; 11 (2): 175-179; KARDINAL, C.G., DONEGAN, W.L., Second cancers after prolonged adjuvant thiotepa for operable carcinoma of the breast, Cancer, 15 Apr. 1980; 45 (8): 2042-2046.
6. Impairment of the central nervous system.
MENA, H., GARCIA, J.H., VELANDIA, F., Central and peripheral myelinopathy associated with systemic neoplasia and chemotherapy, Cancer, Nov. 1981; 48 (8): 1724-1737.
7. Miscellanea: headache, fever, e.a.
ARCHIMBAUD, J.P. ù CALCAT, P., MARTEL, J.P., Pancytopenie spontanément curable due au thiotépa intra-vésical, J. Urol. Nephrol. (Paris), Dec. 1973; 79 (12 Pt. 2): 487-488; KACZMAREK, A., Serious complications following topical administration of thio-tepa in a patient with bladder carcinoma (Polish), Wiad. Lek., 15 Apr. 1978; 31 (8): 547-550; BENNET, E.J., SCHMIDT, G.B., PATEL, K.P., Muscle relaxants, myasthenia and mustards?, Anesthesiology, Mar. 1977; 46 (3): 220-221.
1.4. MITOTANE
(orthopara D.D.D.; o.p. D.D.D.)Chemical denomination: 1,1-dichloro-2-(2-chloro-phenyl) 2-(4-chlorophenyl)-ethane. (NSC 38721).
Action: inhibits the adrenal-steriodo-genesis.
Brands: LYSODREN® (Calbiochem), MITOTANUM® (INN).
Side effects:
Digestive upsets: vomiting, nausea, diarrhoea.
Miscellanea:
Sparagana M, Primary hypogonadism associated with o,p' DDD (mitotane) therapy, J Toxicol Clin Toxicol (UNITED STATES) 1987 25 (6) p463-72; Marechaud R; Boissonnot M; Holderer-Fieuzal S; Gouet D; Boissonnot L , Idiopathic intracranial hypertension during treatment of Cushing's disease with mitotane (letter), Presse Med (FRANCE) Dec 12 1987 16 (42) p2131 ;
1.5. PROCARBAZINE.
Chemical denomination: 1-methyl-2-para isoprpopyl-carbamyl-benzyl-hydrazinechlorohydrate; 1-(4-isopropylcarbamoyl-benzyl)-2-methyl-hydrazine. (NSC 77213).
Action: by inhibiting the synthesis of nucleic acids.
Brands: NATULAN®, PROCARBAZINUM®, IBENZMETHYZIN®, METHYLHYDRAZINE®, MATULANE®, NATULANAR®.
Side effects:
Bramswig JH; Heimes U; Heiermann E; Schlegel W; Nieschlag E; Schellong G, The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence, Cancer (UNITED STATES) Mar 15 1990 65 (6) p1298-302 ; Akyol H; Sarialioglu F; Buyukpamukcu M; Akyuz C , Cytotoxic drug-induced fever: a report on procarbazine-induced hyperpyrexia, Med Pediatr Oncol (UNITED STATES) 1990 18 (2) p173-5; Carneiro PC; Pereira ED; Mitteldorf CS; Martinez GA; Beitler B; Pozzi DH , Acute myeloid leukemia after treatment of Hodgkin's disease, Rev Hosp Clin Fac Med Sao Paulo (BRAZIL) Mar-Apr 1989 44 (2) p87-90 ; Akiyoshi T; Kimura N; Hisano S; Kawara T; Morioka E; Ishibashi M; Kyoshoin K; Kikuchi M; Okumura M , Secondary leukemia (AML) with TcR beta rearrangement, Rinsho Ketsueki (JAPAN) Aug 1989 30 (8) p1304-9 ; Boccaccio P; Rosa F; Casciaro S; D'Elia P; Romagnoli M; Ghio R , Acute leukemia in patients treated for Hodgkin's disease, Recenti Prog Med Jan 1988 79 (1) p32-7 ; Sagher D; Karrison T; Schwartz JL; Larson R; Meier P; Strauss B , Low O6-alkylguanine DNA alkyltransferase activity in the peripheral blood lymphocytes of patients with therapy-related acute nonlymphocytic leukemia, Cancer Res Jun 1 1988 48 (11) p3084-9; Rao SV; Murugesan K; Vij U; Sarin R; Kapur BM , Effect of cancer polychemotherapy on gonadal function in Hodgkin's disease in adult men, Indian J Med Res Jan 1988 87 p37-41 ; Price P; Thompson H; Bessell EM; Bloom HJ , Renal impairment following the combined use of high-dose methotrexate and procarbazine, Cancer Chemother Pharmacol 1988 21 (3) p265-7; Lauta VM; Valerio G; Greco A; Capece Minutolo M, Early-onset diagnosis of lung toxicity caused by cyclophosphamide, melphalan and procarbazine therapy, Tumori Aug 31 1987 73 (4) p351-8;
1.6. DACARBAZINE
Chemical denomination: 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide. (NSC 45388).
Brands: DETICENE® (Bellon), DACARBAZINUM® (INN), DTIC-Dome® .
1.7. CIS-PLATINUM (CARBOPLATINE).
Chemical denomination: CIS-PLATINUM: cis-diamminedichloroplatinum (NSC 119875); CARBOPLATINE: cis-diammine-(1,1-cyclobutanedi-carboxylato)platina(II) (NSC 241240).
Action:
Brands: ALBIPLATIN® (Abic), CISPLATINE ® (Lederle), CISPLATINUM® (INN), PLATINOL® (Bristol-Myers), PLATISTINE® (Labohain), PLATOSIN® (Pharmachemie), PARAPLATIN® (Bristol-Myers), PARAPLATINE® (Bristol-Myers), CISPLATYL® (Bellon, Rhône-Poulenc), CITOPLATINO® (Rhône-Poulenc), NEOPLATIN® (Bristol-Myers), PLACIS® (Wasserman), PLATAMINE ® (Farmitalia), PLATIBLASTIN® (Farmitalia), PLATINEX® (Bristol), PLATISTIL® (Farmitalia) .
Side effects:
Zeger G; Smith L; McQuiston D; Goldfinger D, Cisplatin-induced nonimmunologic adsorption of immunoglobulin by red cells, Transfusion (UNITED STATES) Sep-Oct 1988 28 (5) p493-5; Eskilsson J; Albertsson M, Severe adverse cardiac effects during treatment with cisplatin and 5- fluorouracil; Lakartidningen (SWEDEN) Aug 31 1988 85 (35) p 2734-5 ; Hayashi Y; Iwasaka T; Hachisuga T; Fukuda K; Tanaka T; Matsuo N; Sugimori H , Antiemetic efficacy of high-dose metoclopramide, diphenhydramine, methylprednisolone and diazepam on chemotherapy-induced emesis in gynecological malignancy, Nippon Sanka Fujinka Gakkai Zasshi (JAPAN) Jul 1988 40 (7) p875-9 ; Maeta M; Koga S; Shimizu N; Hamazoe R; Murakami A; Ishiguro M; Sawada T , Intra-hepato-arterial chemotherapy with CDDP and 5-FU for metastases to the liver from colorectal and gastric cancers, Eur J Cancer Clin Oncol Jul 1988 24 (7) p1199-203; Barton C; Duchesne G; Williams M; Fisher C; Horwich A, The impact of hydronephrosis on renal function in patients treated with cisplatin-based chemotherapy for metastatic nonseminomatous germ cell tumors, Cancer Oct 1 1988 62 (7) p1439-43; Hamazoe R; Koga S; Maeda M; Shimizu N; Shimizu T; Sawata T; Ishiguro M; Inoue Y; Wakatsuki T; Murakami A , Hepatic arterial chemotherapy combined with hyperthermia or arterial embolization in unresectable liver tumor, Gan To Kagaku Ryoho Aug 1988 15 (8 Pt 2) p2590-5; Okamoto T; Masahashi T; Ogawa A; Higuchi K; Sawaguchi K; Yabushita H; Noguchi M; Ishihara M , Intra-arterial cis-platinum in the treatment of squamous cell carcinoma of the cervix, Gan To Kagaku Ryoho Aug 1988 15 (8 Pt 2) p2448-52; Cirera L; Gay M; Tome T; Marti M; Huguet J; Pla R, Administration of high doses of cisplatin in 20-minute infusions, Rev Clin Esp (SPAIN) Mar 1988 182 (4) p192-5; Calvert AH; Horwich A; Newlands ES; Begent R; Rustin GJ; Kaye SB; Harris AL; Williams CJ; Slevin ML, Carboplatin or cisplatin? [letter], Lancet (ENGLAND) Sep 3 1988 2 (8610) p577-8; Bostrom B , Severe ileus from cisplatin and vinblastine infusion in neuroblastoma [letter], J Clin Oncol Aug 1988 6 (8) p1356; Bosl GJ; Geller NL; Bajorin D; Leitner SP; Yagoda A; Golbey RB; Scher H; Vogelzang NJ; Auman J; Carey R; et al , A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors, J Clin Oncol Aug 1988 6 (8) p1231-8 ; Glenn LD; Armitage JO; Goldsmith JC; Sorensen S; Howe D; Weisenberger DD , Pulmonary emboli in patients receiving chemotherapy for non-Hodgkin's lymphoma, Chest Sep 1988 94 (3) p589-94; Mavichak V; Coppin CM; Wong NL; Dirks JH; Walker V; Sutton RA , Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man, Clin Sci (ENGLAND) Aug 1988 75 (2) p203-7 ; Carmichael J; Cantwell BM; Edwards CM; Rapeport WG; Harris AL The serotonin type 3 receptor antagonist BRL 43694 and nausea and vomiting induced by cisplatin, Br Med J [Clin Res] (ENGLAND) Jul 9 1988 297 (6641) p110-1; Suzumori K; Yasui Y; Suzumori K; Yagami Y; Seki T , Comparison of methods for evaluating the nephrotoxicity of cisplatin, Gan To Kagaku Ryoho Aug 1988 15 (8) p2251-6 ; Roth BJ; Einhorn LH; Greist A , Long-term complications of cisplatin-based chemotherapy for testis cancer, Semin Oncol (UNITED STATES) Aug 1988 15 (4) p345-50 ; Stefenelli T; Kuzmits R; Ulrich W; Glogar D ,Acute vascular toxicity after combination chemotherapy with cisplatin, vinblastine, and bleomycin for testicular cancer, Eur Heart J May 1988 9 (5) p552-6; Agostinucci WA; Gannon RH; Golub GR; Martin RS; Schauer PK; Dinonno EB , Continuous i.v. infusion versus multiple bolus doses of metoclopramide for prevention of cisplatin-induced emesis, Clin Pharm (UNITED STATES) Jun 1988 7 (6) p454-7; Brechot JM; Dupeyron JP; Guyon F; Delfour C; Delattre C; Lebeau B; Rochemaure J, Dosage adjustment of metoclopramide for controlling vomiting induced by cisplatin: pharmacokinetic approach, Presse Med Jun 4 1988 17 (22) p1147-9; Bindi M; Pepi F; Sebaste L; Tucci E; Pirtoli L , Combination of glucagon and low-dose metoclopramide in management of cisplatin-induced nausea and vomiting [letter], J Natl Cancer Inst (UNITED STATES) Aug 17 1988 80 (12) p973; Walker RW; Cairncross JG; Posner JB , Cerebral herniation in patients receiving cisplatin, J Neurooncol (UNITED STATES) 1988 6 (1) p61-5; Daugaard G; Abildgaard U; Holstein-Rathlou NH; Bruunshuus I; Bucher D; Leyssac PP , Renal tubular function in patients treated with high-dose cisplatin, Clin Pharmacol Ther (UNITED STATES) Aug 1988 44 (2) p164-72; Tsujii T; Tari K; Yonese J; Kojima S , Antiemetic effect of timiperone and methylprednisolone in cisplatin- induced emesis, Gan To Kagaku Ryoho (JAPAN) Jul 1988 15 (7) p2101-5; Nogueras Gimeno MA; Espuela Orgaz R; Abad Menor F; Martinez Perez E; Amo Garcia A, Allergic reactions to the intravesical instillation of cisplatin, Actas Urol Esp (SPAIN) Sep-Oct 1987 11 (5) p461-4; Lechner W; Zechmann W; Mayr P; Reider W; Marth C , Zur Frage der Kardiotoxizitat von Epirubicin--Cisplatin, Zentralbl Gynakol 1988 110 (7) p429-32; Grunberg SM; Ehler E; McDermed JE; Akerley WL , Oral metoclopramide with or without diphenhydramine: potential for prevention of late nausea and vomiting induced by cisplatin, J Natl Cancer Inst (UNITED STATES) Aug 3 1988 80 (11) p864-8; Samuels BL; Kahn CE Jr; Messersmith RN; Vogelzang NJ; Simon , Brachial plexopathy after intraarterial cisplatin [letter], MA J Clin Oncol (UNITED STATES) Jul 1988 6 (7) p1204; Le Moing P; Bauduer F; Genot JY; Peny AM; Tanguy A , Signe de Lhermitte apres traitement par la cisplatine, Presse Med (FRANCE) May 7 1988 17 (17) p875 ; Rosenblatt E; Lev LM; Robinson E , High-dose dexamethasone and high-dose metoclopramide versus high-dose dexamethasone and sulpiride in the management of cisplatin-induced emesis, Oncology 1988 45 (4) p297-9; Chen JT; Yamashiro T; Shimizu Y; Kuo TC; Nakayama K; Teshima H; Hirai Y; Hamada T; Fujimoto I; Yamauchi K; et al , Renal toxicity by intraperitoneal administration of CDDP, Nippon Sanka Fujinka Gakkai Zasshi (JAPAN) May 1988 40 (5) p534-40; Gerritsen van der Hoop R; de Koning P; Boven E; Neijt JP; Jennekens FG; Gispen WH , Efficacy of the neuropeptide ORG.2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats, Eur J Cancer Clin Oncol (ENGLAND) Apr 1988 24 (4) p637-42; Jakubowski AA; Kemeny N, Hypotension as a manifestation of cardiotoxicity in three patients receiving cisplatin and 5-fluorouracil, Cancer (UNITED STATES) Jul 15 1988 62 (2) p266-9; Forastiere AA; Belliveau JF; Goren MP; Vogel WC; Posner MR; O'Leary GP Jr , Pharmacokinetic and toxicity evaluation of five-day continuous infusion versus intermittent bolus cis-diamminedi-chloroplatinum(II) in head and neck cancer patients, Cancer Res (UNITED STATES) Jul 1 1988 48 (13) p3869-74; Walther PJ; Rossitch E Jr; Bullard DE , The development of Lhermitte's sign during cisplatin chemotherapy. Possible drug-induced toxicity causing spinal cord demyelination, Cancer Nov 1 1987 60 (9) p2170-2; Carr BI; Blayney DW; Goldberg DA; Braly P; Metter GE; Doroshow JH , High doses of prochlorperazine for cisplatin-induced emesis. A prospective, random, dose-response study, Cancer Nov 1 1987 60 (9) p2165-9 ; Hida S; Nishimura K; Nishio Y; Okada Y; Okada K; Yoshida O , Hypomagnesemia following chemotherapy of disseminated testicular tumors, Hinyokika Kiyo Jan 1988 34 (1) p52-60; Behling H; Spieske C; Krafft W, Ototoxische Nebenwirkungen bei Ovarialkarzinom-patienten, die mit Cisplatin behandelt wurden, Zentralbl Gynakol 1988 110 (5) p277-82; Pommier RF; Moseley HS; Cohen J; Huang CS; Townsend R; Fletcher WS , Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft-tissue sarcoma and melanoma of the extremities, Am J Surg May 1988 155 (5) p667-71; Bellin SL; Selim M , Cisplatin-induced hypomagnesemia with seizures: a case report and review of the literature, Oncol (UNITED STATES) May 1988 30 (1) p104-13; Mollman JE; Glover DJ; Hogan WM; Furman RE , Cisplatin neuropathy. Risk factors, prognosis, and protection by WR-2721, Cancer Jun 1 1988 61 (11) p2192-5; Jorkasky DK; Singer I , Drug-induced tubulo-interstitial nephritis: special cases, Semin Nephrol (UNITED STATES) Mar 1988 8 (1) p62-71; Kobayashi H , The effect of metoclopramide, dexamethasone and antihistamine in the prevention of PAC chemotherapy-induced emesis, Nippon Sanka Fujinka Gakkai Zasshi Feb 1988 40 (2) p153-9; Murugesan K; Rao SV; Vij U; Sarin R; Kapur BM , Effect of chemotherapy on gonadal function in women with breast cancer, Indian J Med Res Jan 1988 87 p42-5; Ostchega Y; Donohue M; Fox N , High-dose cisplatin-related peripheral neuropathy, Cancer Nurs (UNITED STATES) Feb 1988 11 (1) p23-32; Mariette X; Paule B; Bennet P; Clerc D; Bisson M; Massias P , Cisplatin and hyponatremia [letter], Ann Intern Med (UNITED STATES) May 1988 108 (5) p770-1; Hoshino K; Mizushima Y; Yano S; Kitagawa M , An autopsied case of pulmonary carcinoma with perforation peritonitis due to metastatic tumor necrosis at the jejunum caused by chemotherapy, Gan No Rinsho Apr 1988 34 (4) p491-6; Kris MG; Gralla RJ; Clark RA; Tyson LB; Groshen S , Control of chemotherapy-induced diarrhea with the synthetic enkephalin BW942C: a randomized trial with placebo in patients receiving cisplatin, J Clin Oncol Apr 1988 6 (4) p663-8 ; van der Hulst RJ; Dreschler WA; Urbanus NA , High frequency audiometry in prospective clinical research of ototoxicity due to platinum derivatives, Ann Otol Rhinol Laryngol Mar-Apr 1988 97 (2 Pt 1) p133-7; Taniwaki M; Yokota S; Nishida K; Tsuda S; Edagawa J; Misawa S; Takino T; Abe T , A clinical trial to prevent the renal toxicity of cisplatin by administration of bismuth subnitrate, Gan To Kagaku Ryoho Mar 1988 15 (3) p531-3; Socinski MA; Garnick MB , Acute pancreatitis associated with chemotherapy for germ cell tumors in two patients, Ann Intern Med Apr 1988 108 (4) p567-8 ; Quinn SF; Frau DM; Saff GN; Kavanagh J; Roberts W; Cavanagh D; Clark RA, Neurologic complications of pelvic intraarterial chemoembolization performed with collagen material and cisplatin, Radiology (UNITED STATES) Apr 1988 167 (1) p55-7 ; Sagawa M; Takahashi S; Usuda K; Kamma K; Satoh M; Ohta S; Nagamoto N; Imai T; Saitoh Y; Suda H; et al, Interstitial pneumonia after CMC (CDDP, MMC, CPM) therapy, Gan No Rinsho Feb 1988 34 (2) p150-4; Walther PJ; Rossitch E Jr; Bullard DE , The development of Lhermitte's sign during cisplatin chemotherapy. Possible drug-induced toxicity causing spinal cord demyelination, Cancer Nov 1 1987 60 (9) p2170-2; Weinblatt ME; Kahn E; Scimeca PG; Kochen JA , Hemolytic uremic syndrome associated with cisplatin therapy, Am J Pediatr Hematol Oncol (UNITED STATES) Winter 1987 9 (4) p295-8; Kupersmith MJ; Frohman LP; Choi IS; Foo SH; Hiesinger E; Berenstein A; Wise A; Carr RE; Ransohoff J , Visual system toxicity following intra-arterial chemotherapy, Neurology (UNITED STATES) Feb 1988 38 (2) p284-9; Brohee D; Chalet J; Cornil Y; d'Inverno E , Intraperitoneal haemorrhage during intraperitoneal cisplatin therapy and concomitant systemic heparin therapy, Neth J Med (NETHERLANDS) Dec 1987 31 (5-6) p251-2; Takada S; Azukizawa S; Kubota Y; Masuda M , Ileus due to extensive adhesion formation after intraperitoneal chemotherapy using cisplatinum, Asia Oceania J Obstet Gynaecol (JAPAN) Dec 1987 13 (4) p445-9; Umeki S; Watanabe M; Yagi S; Soejima R , Supplemental fosfomycin and/or steroids that reduce cisplatin-induced nephrotoxicity, Am J Med Sci (UNITED STATES) Jan 1988 295 (1) p6-10 ; Shibuya K; Satoh M; Hasegawa T; Naganuma A, Protective effect of Chinese medicines on toxic side effects of cis- diamminedichloroplatinum in mice, Imura N Yakugaku Zasshi Jul 1987 107 (7) p511-6; Mendoza EA; Thomas LC; Sutherland CM , Acute myelocytic leukemia following radiation and chemotherapy for esophageal carcinoma, J La State Med Soc Nov 1987 139 (11) p30-2; Sridhar KS; Barreras L; Saldana MJ; Manten H , Respiratory tract fistulae in recurrent aerodigestive cancers after chemotherapy, Cancer (UNITED STATES) Jan 15 1988 61 (2) p247-51; Cohen SC; Mollman JE , Cisplatin-induced gastric paresis, J Neurooncol (UNITED STATES) 1987 5 (3) p237-40 ; Tange RA , An abnormality in the human cochlear vasculature in a case of cis-platinum ototoxicity, Acta Otolaryngol Suppl (Stockh) 1987 436 p133-7 ; Caston J; Doinel L , Comparative vestibular toxicity of dibekacin, habekacin and cisplatin, Acta Otolaryngol (Stockh) (SWEDEN) Sep-Oct 1987 104 (3-4) p315-21; Daugaard GK; Petrera J; Trojaborg W , Electrophysiological study of the peripheral and central neurotoxic effect of cis-platin, Acta Neurol Scand (DENMARK) Aug 1987 76 (2) p86-93 ; Freedman MS; Schneiderman JH; Turley J; DePetrillo AD , Neurologic complications following intra-arterial cis-platinum chemotherapy [letter], Can J Neurol Sci (CANADA) Aug 1987 14 (3) p325; Ratain MJ; Kaminer LS; Bitran JD; Larson RA; Le Beau MM; Skosey C; Purl S; Hoffman PC; Wade J; Vardiman JW; et al , Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung, Blood Nov 1987 70 (5) p1412-7 ; Nino S; Umehara H; Inoue I; Tamura T; Sasaki Y; Sakurai M; Shinkai T; Eguchi K; Saijo N; Suemasu K , A randomized controlled trial of acute and delayed cisplatin-induced emesis with metoclopramide, dexamethasone and prochlorperazine, Gan To Kagaku Ryoho Oct 1987 14 (10) p2881-4 ; Wang LW; Zhang SW; Yang T; Deng XJ; Xu GY; Li WC , Nephrotoxicity of cisplatin, Chung Kuo Yao Li Hsueh Pao Mar 1987 8 (2) p166-9 ; Soin KS; Agarwal GN; Dwivedi M; Tandon VK; Dwivedi S; Sarkar SS , Assessment of renal biochemical and histopathological parameters in predicting reversibility of cis-platinum nephrotoxicity, Indian J Cancer Dec 1986 23 (4) p197-205 ; Pollera CF; Ameglio F; Nardi M; Marolla P; Carlini P; Frasca AM , Dose and schedule effects of cisplatin on the related acute iron changes, Oncology (SWITZERLAND) 1990 47 (2) p133-8; Cirami C; Bianchi AM; Galigani P; Gadducci A; Colombi L; Facchini V; Palla R , Cisplatin nephrotoxicity: effects on fractional excretion of sodium and enzymuria, Minerva Med (ITALY) Jan-Feb 1990 81 (1-2) p79-86 ; Daugaard G , Cisplatin nephrotoxicity: experimental and clinical studies, Dan Med Bull (DENMARK) Feb 1990 37 (1) p1-12; Tsutsumi T; Ozawa Y; Kawakami A; Fujii H; Asamoto H , Acute myocardial infarction induced by lung cancer chemotherapy with cisplatin and etoposide, Gan To Kagaku Ryoho (JAPAN) Mar 1990 17 (3 Pt 1) p413-7; Bennett WM; Porter GA , Nephrotoxicity of common drugs used by urologists, Urol Clin North Am (UNITED STATES) Feb 1990 17 (1) p145-56; Gardner G; Mesler D; Gitelman HJ , Hemolytic uremic syndrome following cisplatin, bleomycin, and vincristine chemotherapy: a report of a case and a review of the literature, Ren Fail (UNITED STATES) 1989 11 (2-3) p133-7; Reed E; Evans MK , Acute leukemia following cisplatin-based chemotherapy in a patient with ovarian cancer [letter], J Natl Cancer Inst (UNITED STATES) Mar 7 1990 82 (5) p431-2; Bruck W; Heise E; Friede RL , Leukoencephalopathy after cisplatin therapy, Clin Neuropathol (GERMANY, WEST) Nov-Dec 1989 8 (6) p263-5; Bissett D; Cornford EJ; Sokal M , Hyponatraemia following cisplatin chemotherapy, Acta Oncol (SWEDEN) 1989 28 (6) p823; Shimamura Y; Chikama M; Tanimoto T; Kawakami Y; Tsutsumi A , Optic nerve degeneration caused by supraophthalmic carotid artery infusion with cisplatin and ACNU, J Neurosurg (UNITED STATES) Feb 1990 72 (2) p285-8 ; Walker DA; Waters KD , Treatment-related ototoxicity [letter], J Clin Oncol (UNITED STATES) Jan 1990 8 (1) p179-8; Lechner W; Soldner E; Sachsenmaier M; Philadelphy H; Jarosch E , Magnesium deficiency caused by epirubicin/cisplatin, Zentralbl Gynakol (GERMANY, EAST) 1989 111 (21) p1438-40; Elderson A; Gerritsen van der Hoop R; Haanstra W; Neijt JP; Gispen WH; Jennekens FG , Vibration perception and thermoperception as quantitative measurements in the monitoring of cisplatin induced neurotoxicity., J Neurol Sci (NETHERLANDS) Nov 1989 93 (2-3) p167-74; Daugaard G; Abildgaard U , Cisplatin nephrotoxicity. A review., Cancer Chemother Pharmacol (GERMANY, WEST) 1989 25 (1) p1-9; Moul JW; Robertson JE; George SL; Paulson DF; Walther PJ , Complications of therapy for testicular cancer, J Urol (UNITED STATES) Dec 1989 142 (6) p1491-6 ; Gouge SF; Tietjen DP; Moore J Jr , Irreversible renal failure after intraperitoneal cisplatin administration. A case report., J Reprod Med (UNITED STATES) Nov 1989 34 (11) p931-3 ; Chambers SK; Chopyk RL; Chambers JT; Schwartz PE; Duffy TP , Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer, Cancer (UNITED STATES) Dec 15 1989 64 (12) p2459-61; Rodriguez M; Solanki DL; Whang R , Refractory potassium repletion due to cisplatin-induced magnesium depletion, Arch Intern Med (UNITED STATES) Nov 1989 149 (11) p2592-4 ; Brodsky A; Aparici I; Argeri C; Goldenberg D , Stevens-Johnson syndrome, respiratory distress and acute renal failure due to synergic bleomycin-cisplatin toxicity, J Clin Pharmacol (UNITED STATES) Sep 1989 29 (9) p821-3; Wallace WH; Shalet SM; Crowne EC; Morris-Jones PH; Gattamaneni HR; Price DA , Gonadal dysfunction due to cis-platinum., Med Pediatr Oncol (UNITED STATES) 1989 17 (5) p409-13;
1.8. MANNOMUSTINE HYDROCHLORIDE.
Chemical denomination: bis-(ß-chloroethylamino) 1,6-desoxy-1,6 D-mannitol chlorohydrate. (NSC 9698).
Brands: DEGRANOL® (Landerlan, Sinclair).
1.9. HEXAMETHYLMELAMINE
Chemical denomination: 2,4,6-tris(dimethylamino)-1,3,5-triazine. (NSC 13875).
Action: zoals Thio-Tepa.
Brands: HEXASTAT® (Rhône-Poulenc), HEXINAWAS® (Wasserman).
1.10. TRETAMINE
Chemical denomination: 2,4,6-tris(aziridin-1-yl-)-1,3,5-triazine. (NSC 9706)
Action: like Thio-Tepa.
Brands: not commercialized.
1.11. TROFOSFAMIDE
Chemical denomination: 3-(2-chloroethyl)-2-[bis-(2-chloroethyl)-amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide. (NSC 109723).
Action: like cyclofosfamide.
Brands: IXOTEN® (Asta, Schering, Noristan), TRIFOSFAMIDUM® (INN).
1.12. IFOSFAMIDE
Chemical denomination: 3-(2-chloroethyl)-2-{(2-chloroethyl)-amino}-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide. (NSC 109724).
Brands: HOLOXAN® (Lucien, Schering, Degussa, Asta), IFOSFAMIDUM® (INN), MITOXANA® (Boehringer), TRONOXAL® (Funk).
Side effects:
Lewis LD; Meanwell CA , Ifosfamide pharmacokinetics and neurotoxicity [letter], Lancet (ENGLAND) Jan 20 1990 335 (8682) p175-6; Danesh MM; De Giorgio CM; Beydoun SR; Kemp RA, Ifosfamide encephalopathy, J Toxicol Clin Toxicol (UNITED STATES) 1989 27 (4-5) p293-8 ; Goren MP; Pratt CB; Viar MJ , Tubular nephrotoxicity during long-term ifosfamide and mesna therapy, Cancer Chemother Pharmacol (GERMANY, WEST) 1989 25 (1) p70-2; Goren MP; Pratt CB; Meyer WH; Wright RK; Dodge RK; Viar MJ, Mesna excretion and ifosfamide nephrotoxicity in children, Cancer Res (UNITED STATES) Dec 15 1989 49 (24 Pt 1) p7153-7; Watkin SW; Husband DJ; Green JA; Warenius HM , Ifosfamide encephalopathy: a reappraisal, Eur J Cancer Clin Oncol (ENGLAND) Sep 1989 25 (9) p1303-10 ; Kandylis K; Vassilomanolakis M; Tsoussis S; Efremidis AP, Ifosfamide cardiotoxicity in humans, Cancer Chemother Pharmacol (GERMANY, WEST) 1989 24 (6) p395-6; Gieron MA; Barak LS; Estrada J, Severe encephalopathy associated with ifosfamide administration in two children with metastatic tumors, Neurooncol (UNITED STATES) 1988 6 (1) p29-30 ; Ghosn M; Carde P; Leclerq B; Flamant F; Friedman S; Droz JP; Hayat M , Ifosfamide/mesna related encephalopathy: a case report with a possible role of phenobarbital in enhancing neurotoxicity, Bull Cancer (Paris) (FRANCE) 1988 75 (4) p391-2 ; Beuzeboc P; Dorval T; Garcia-Giralt E; Jouve M; Livartowski A; Palangie T; Scholl S; Pouillart P , Encephalopathy caused by an ifosfamide-mesna combination (letter), Presse Med (FRANCE) Apr 2 1988 17 (12) p591-2 ; Husband DJ; Watkin SW, Fatal hypokalaemia associated with ifosfamide/mesna chemotherapy [letter] , Lancet (ENGLAND) May 14 1988 1 (8594) p1116 ; Choonara IA; Overend M; Bailey CC , Blurring of vision due to ifosfamide [letter], Cancer Chemother Pharmacol (GERMANY, WEST) 1987 20 (4) p349 ; Pratt CB; Goren MP , Ifosfamide/mesna and hematuria [letter], Cancer Treat Rep Nov 1987 71 (11) p1124-5 ;
1.13. MITOCLOMINE
2. Antibiotics.
The remedies described in this chapter are called antibiotics, because they are all extracted from micro-organisms. However, their action in cancer differs and happens for a first group through a selective binding with DNA, creating complexes who result in inhibiting the transcription, or, to say it in other words, who prevent prevent sythesis of RNA.
The action of a second group of antibiotics is strongly related to the first one : here the protein synthesis is slowed down on the understanding that the blocking happens at the same time as the formation of the RNAt - RNAm complex (activated omino acid on the ribosome complex). Certainly these remedies prevent the synthesis of whole proteins.
A third group of antibiotics acts through radiomimetics where cell division is slowed down without interfering with the biosynthesis of nucleic acids.
I.Remedies inhibiting transcription.
2.1. CACTINOMYCINE
2.2. DACTINOMYCINEClan: Streptomyces genus, streptomyces parvullus. (NSC 3053).
Brands: LYOVAC-COSMEGEN® (Merck Sharpe & Dohme), DACTINOMYCINUM® (INN)
Side effects:
Dozono H; Nakamura K; Motoya T; Nakamura S; Shinmura R; Miwa K; Ishibashi M; Nagata Y Prevention of stomatitis induced by anti-cancer drugs, Gan To Kagaku Ryoho (JAPAN) Oct 1989 16 (10) p3449-51 ; Hayashi Y; Ohi R; Konno T; Tsuchiya S; Muraosa Y; Yaoita S; Watanabe T , Effect of VAB-6 combination chemotherapy on malignant germ cell tumours in childhood, Z Kinderchir (GERMANY, WEST) Aug 1989 44 (4) p208-12 ; Fernandez H; Diallo A; Baume D; Papiernik E , Anhydramnios and cessation of fetal growth in a pregnant mother with polychemotherapy during the second trimester, Prenat Diagn (ENGLAND) Sep 1989 9 (9) p681-2;
2.3. DAUNOMYCINE, RUBIDOMYCINE
or DAUNORUBICINEClan: Streptomyces peucetius, streptomyces coeruleorubidus. (NSC 82151).
Brands: CERUBIDINE® (Rhône-Poulenc, Bellon, Wyeth, Specia), DAUNORUBICINUM® (INN), CERUBIDIN® (May & Baker, Rhône-Poulenc), DAUNOBLASTIN® (Farmitalia), DAUNOBLASTINA® (Farmitalia).
2.4. DOXORUBICINE HYDROCHLORIDE
Clan: Streptomyces ceruleo-rubidus, streptomyces peucetius var. coesius. (NSC 123127).
Brands: ADRIABLASTINA (HCL)® (Labohain), DOXORUBICINUM® (INN), ADRIAMYCIN® (Farmitalia), ADRIBLASTIN® (Farmitalia), ADRIBLASTINE® (Bellon, Farmitalia), FARMIBLASTINA® (Farmitalia).
Side effects:
Hamlin RL , Clinical toxicology of cardiovascular drugs., Vet Clin North Am Small Anim Pract (UNITED STATES) Mar 1990 20 (2) p469-81; Dmochowski R; Rudy DC , Bladder contracture following intravesical doxorubicin therapy: case report and a review of the literature, J Urol (UNITED STATES) Apr 1990 143 (4) p816-8 ; Twelves CJ; Chaudary MA; Reidy J; Richards MA; Rubens RD, Toxicity of intra-arterial doxorubicin in locally advanced breast cancer, Cancer Chemother Pharmacol (GERMANY, WEST) 1990 25 (6) p459-62; Bramswig JH; Heimes U; Heiermann E; Schlegel W; Nieschlag E; Schellong G, The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence., Cancer (UNITED STATES) Mar 15 1990 65 (6) p1298-302; Rusignuolo F; Palumbo FP; Bellisi M; Romano P; Anselmo G; Cortese LF , Clinico-morphologic correlations of lesions induced by adriamycin administered in the thoracic aorta, G Ital Oncol (ITALY) Oct-Dec 1989 9 (4) p145-56 ; Sen P; Bailey NM; Hagemeister FB; Liang JC , Induction of chromosome breaks and sister chromatid exchanges in patients with Hodgkin's disease by two combination chemotherapy regimens of different leukemogenic potential, Cancer Res (UNITED STATES) Feb 1 1990 50 (3) p558-62; Shapira J; Gotfried M; Lishner M; Ravid M , Reduced cardiotoxicity of doxorubicin by a 6-hour infusion regimen. A prospective randomized evaluation, Cancer (UNITED STATES) Feb 15 1990 65 (4) p870-3 ; Goorin AM; Chauvenet AR; Perez-Atayde AR; Cruz J; McKone R; Lipshultz SE , Initial congestive heart failure, six to ten years after doxorubicin chemotherapy for childhood cancer, J Pediatr (UNITED STATES) Jan 1990 116 (1) p144-7 ; Arena FP; Sherlock S , Doxorubicin hypersensitivity and clindamycin [letter], Ann Intern Med (UNITED STATES) Jan 15 1990 112 (2) p150 ; Ogilvie GK; Richardson RC; Curtis CR; Withrow SJ; Reynolds HA; Norris AM; Henderson RA; Klausner JS; Fowler JD; McCaw D , Acute and short-term toxicoses associated with the administration of doxorubicin to dogs with malignant tumors, J Am Vet Med Assoc (UNITED STATES) Dec 1 1989 195 (11) p1584-7 ; Sonneveld P; Kurth KH; Hagemeyer A; Abels J, Secondary hematologic neoplasm after intravesical chemotherapy for superficial bladder carcinoma., Cancer (UNITED STATES) Jan 1 1990 65 (1) p23-5; Curran CF; Luce JK, Ocular adverse reactions associated with adriamycin (doxorubicin), Am J Ophthalmol (UNITED STATES) Dec 15 1989 108 (6) p709-11; Simon DL, Comment: doxorubicin extravasions [letter] , DICP (UNITED STATES) Nov 1989 23 (11) p928; Druet P; Kleinknecht D , Toxic glomerulonephritis, Presse Med (FRANCE) Nov 11 1989 18 (37) p1840-5 ; Chambers SK; Chopyk RL; Chambers JT; Schwartz PE; Duffy TP, Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer, Cancer (UNITED STATES) Dec 15 1989 64 (12) p2459-61; Sobotka-Plojhar MA; Daniels O; Rohmer J; Veerman AJ; Lippens R; van Lier H , The effect of the anthracycline derivative doxorubicin on myocardial function in children, Ned Tijdschr Geneeskd (NETHERLANDS) Jul 8 1989 133 (27) p1367-70 ;
2.5. ADRIAMYCINE
Clan: Streptomyces pecetius caesius
Brands: ADRIBLASTINE®
2.6. MITHRAMYCINE
Clan: Streptomyces plicatus
Brands: MITHRACIN®
2.7. MITOMYCINE D
Clan: Streptomyces tanashiensis, streptomyces caespitosus. (NSC 26980).
Brands: AMETYCINE® (Choay), MITOMYCIN-C® (Sigma), MITOMYCINE® (Belgium), MUTAMYCIN® (Bristol).
Side effects:
Saito R; Tsuchiya S; Ishizuka T; Fueki N; Ezawa K; Minato K; Nakano H; Takise A; Kurihara M; Fueki R , Clinical effects of cepharanthin (Ceph.) on leukopenia by chemotherapy in lung cancer patients, Nippon Gan Chiryo Gakkai Shi (JAPAN) Dec 20 1989 24 (11) p2587-93 ; Mackintosh J, Cardiopulmonary complications of mitomycin-C [letter], Med J Aust (AUSTRALIA) Jan 1 1990 152 (1) p55; Sonneveld P; Kurth KH; Hagemeyer A; Abels J , Secondary hematologic neoplasm after intravesical chemotherapy for superficial bladder carcinoma, Cancer (UNITED STATES) Jan 1 1990 65 (1) p23-5; Monteagudo J; Pereira A; Roig S; Reverter JC; Ordinas A; Castillo R , Investigation of plasma von Willebrand factor and circulating platelet aggregating activity in mitomycin C-related hemolytic-uremic syndrome, Am J Hematol (UNITED STATES) Jan 1990 33 (1) p46-9 ; Druet P; Kleinknecht D , Toxic glomerulonephritis] Les nephropathies glomerulaires d'origine toxique, Presse Med (FRANCE) Nov 11 1989 18 (37) p1840-5; Farha AJ; Krauss DJ , Renal failure after intravesical mitomycin C, Urology (UNITED STATES) Oct 1989 34 (4) p216-7; Drago PC; Badalament RA; Lucas J; Drago JR , Bladder wall calcification after intravesical mitomycin C treatment of superficial bladder cancer, J Urol (UNITED STATES) Oct 1989 142 (4) p1071-2 ;
2.8. QUINACRINE
See description under 6.8.
II. Remedies inhibiting traduction.
2.9. PUROMYCINE
Clan: Streptomyces alboniger
Brands:
III. Radiomimetic remedies.
2.10. BLEOMYCINE sulphate
Clan: Streptomyces verticillus.
Brands: BLEOMYCINE® (Lundbeck), BLEOMYCINUM® (INN), BLENOXANE® (Bristol-Myers), BLEO-OIL® (Japan), BLEO-S® (Japan), BLOCAMICINA® (Argentina), VERBUBLEN® (Canada).
Side effects:
Jan KY; pin YC; Ho IC; Kao SL; Lee TC, Effects of sodium arsenite on the cytotoxicity of bleomycin, Toxicol Lett (NETHERLANDS) Mar 1990 51 (1) p81-90 ; Hsu TC; Shillitoe EJ; Cherry LM; Lin Q; Schantz SP; Furlong C , Cytogenetic characterization of 20 lymphoblastoid lines derived from human individuals differing in bleomycin sensitivity, In Vitro Cell Dev Biol (UNITED STATES) Jan 1990 26 (1) p80-4; Lin FT , Preclinical pharmacologic evaluation of bleomycin A6, Chung Hua Chung Liu Tsa Chih (CHINA) Jul 1989 11 (4) p257-9 ; Matsumoto H; Furukawa Y; Fujii A; Yamamoto H; Suzuki K; Mashima K; Ohmine H, A study on the toxicity of antineoplastic drugs (bleomycin, peplomycin and cis-diamminedichloroplatinum) by simultaneous administration (Part 1) J Nihon Univ Sch Dent (JAPAN) Dec 1989 31 (4) p597-611 ; Pan QC; Guo HY , The potentiation of the antitumor activity but not toxicity of bleomycin by 3- aminobenzamide, J Antibiot (Tokyo) (JAPAN) Dec 1989 42 (12) p1860-8 ; Steighner RJ; Povirk LF , Effect of in vitro cleavage of apurinic/apyrimidinic sites on bleomycin- induced mutagenesis of repackaged lambda phage, Mutat Res (NETHERLANDS) Feb 1990 240 (2) p93-100 ; Tryka AF, ICRF 187 and polyhydroxyphenyl derivatives fail to protect against bleomycin induced lung injury, Toxicology (IRELAND) Dec 1 1989 59 (2) p127-38; Pohl H; Reidy JA , Vitamin C intake influences the bleomycin-induced chromosome damage assay: implications for detection of cancer susceptibility and chromosome breakage syndromes, Mutat Res (NETHERLANDS) Oct 1989 224 (2) p247-52; Iwanari O; Date Y; Yoshino N; Miyako J; Ryuhkoh K; Moriyama M; Nakayama S; Kitao M, Studies on renal dysfunction after intra-arterial hypertensive chemotherapy (CDDP, PEP) for advanced cancer of the uterine cervix--serum.urinary alpha 1- microglobulin, beta 2-microglobulin and urinary lysozyme, albumin, Nippon Sanka Fujinka Gakkai Zasshi (JAPAN) Feb 1990 42 (2) p115-20; Cortina P; Garrido JA; Tomas JF; Unamuno P; Armijo M, 'Flagellate' erythema from bleomycin. With histopathological findings suggestive of inflammatory oncotaxis, Dermatologica (SWITZERLAND) 1990 180 (2) p106-9; Jensen JL; Goel R; Venner PM , The effect of corticosteroid administration on bleomycin lung toxicity, Cancer (UNITED STATES) Mar 15 1990 65 (6) p1291-7; Gardner G; Mesler D; Gitelman HJ , Hemolytic uremic syndrome following cisplatin, bleomycin, and vincristine chemotherapy: a report of a case and a review of the literature, Ren Fail (UNITED STATES) 1989 11 (2-3) p133-7; Sen P; Bailey NM; Hagemeister FB; Liang JC , Induction of chromosome breaks and sister chromatid exchanges in patients with Hodgkin's disease by two combination chemotherapy regimens of different leukemogenic potential, Cancer Res (UNITED STATES) Feb 1 1990 50 (3) p558-62 ; Leung WH; Lau JY; Chan TK; Kumana CR , Fulminant hyperpyrexia induced by bleomycin, Postgrad Med J (ENGLAND) Jun 1989 65 (764) p417-9; Bellmunt J; Navarro M; Morales S; Jolis L; Carulla J; Knobell H; Vilardell M; Sole LA , Capillary microscopy is a potentially useful method for detecting bleomycin vascular toxicity, Cancer (UNITED STATES) Jan 15 1990 65 (2) p303-9; Vignini M; Miori L; Brusamolino E; Pelfini C , Linear streaking after bleomycin administration [letter], Clin Exp Dermatol (ENGLAND) May 1989 14 (3) p261; Brousil J; Foltynova V; Belohlavek O; Abrahamova J, Detection of functional changes in the myocardium after chemotherapy using radionuclide ventriculography in patients with testicular tumors, Bratisl Lek Listy (CZECHOSLOVAKIA) Sep 1989 90 (9) p637-9; Schantz SP; Hsu TC; Ainslie N; Moser RP , Young adults with head and neck cancer express increased susceptibility to mutagen-induced chromosome damage, JAMA (UNITED STATES) Dec 15 1989 262 (23) p3313-5; Brodsky A; Aparici I; Argeri C; Goldenberg D, Stevens-Johnson syndrome, respiratory distress and acute renal failure due to synergic bleomycin-cisplatin toxicity, J Clin Pharmacol (UNITED STATES) Sep 1989 29 (9) p821-3; Musilova J; Michalova K; Folberova L; Pacovsky V , Chromosome aberrations induced by bleomycin in the lymphocytes of young and old persons, Cas Lek Cesk (CZECHOSLOVAKIA) Sep 8 1989 128 (37) p1166-9 ; Niklander C; Guzman L , Raynaud's phenomenon induced by bleomycin: a clinical case, Rev Med Chil (CHILE) Dec 1988 116 (12) p1302-5;
2.11. STREPTONIGRIN (METHYL ESTER)
Clan: Streptomyces flocculus
Brands:
IV. Miscellaneous
2.12. RUFOCROMOMYCINE
Clan: Streptomyces rufocromogenes
Brands: RUFOCROMOMYCINE®
2.13. STREPTOMYCINE
Clan: Streptomyces
Brands:
2.14. PROFINOMYCINE
Clan: Streptomyces
Brands:
2.15. EPIRUBICINE
Chemical denomination: (1S,3S)-3-gycoloyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphtacenyl 3-amino-2,3,6- trideoxy-a- L-arabino-hexopyranoside.
Brands: FARMORUBICINE HCL)® (Labohain), EPIRIBICINUM® (INN).
2.16. MITOXANTRON
Chemical denomination: 1,4-dihydroxy-5,8-bis{{2-{(2-hydroxyethyl)amino} ethyl}amino}-9,10-antracene-dion.
Action: structurel related to doxorubicine, but the working of its mechanism is insufficiently known.
Brands: MITOXANTRONUM® (INN), NOVANTRONE (Cyanamid).
2.17. PLICAMYCINE.
Clan: streptomyces plicatus.
Brands: MITHRACIN® (Pfizer), PLICAMYCINUM® (INN).
2.18. STREPTOZOCINE.
Clan: streptomyces achromogenes.
Brands: ZANOSAR® (Upjohn), STREPTOZOCINUM® (INN).
2.19. ZORUBICINE
Chemicla denomination: (2S,4S)-{1-[4-(3-amino-2,3,6-trideoxy-a-L-lyxopyranosyloxy)-1,2,3,4,6,11-hexa-hydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxonaphta-ceen-2-yl]ethilideen}hydrazide hydrochloride. (NSC 164011).
Action: is a anthracycline antibiotic derived from daunorubicine that acts like doxorubicine.
Brands: RUBIDAZONE® (Bellon).
2.20. ZINOSTATINE
Clan: from streptomyces carzinostaticus.
Brands: NEOCARZINOSTATUM® (Japan).
2.21. ACLARUBICIN
Clan: from streptomyces galilaeus
Brands: ACLACINOMYCINE® (Bellon), ACLAPLASTIN® (Behringwerke), JACLACIN® (Lundbeck).
Side effects of antibiotics in cancer:
Ruiz Contreras J , New antibiotics in pediatrics, An Esp Pediatr (SPAIN) Dec 1989 31 (6) p515-8; Hoigne R; Jaeger MD; Wymann R; Egli A; Muller U; Hess T; Galeazzi R; Maibach R; Kunzi UP , Time pattern of allergic reactions to drugs, Agents Actions Suppl (SWITZERLAND) 1990 29 p39-58; Committee, Canadian Paediatric Society., Mupirocin in the treatment of impetigo. Infectious Diseases and Immunization, Can Med Assoc J (CANADA) Mar 15 1990 142 (6) p543-4 ; Delmee M , Epidemiological study of the pathogenicity of Clostridium difficile using a new serogrouping method, Acta Gastroenterol Belg (BELGIUM) Nov-Dec 1988 51 (6) p450-8; Colatutto A; Cicuttini L; Pellegrini MA; Rotolo V, Clostridium difficile enterocolitis in subjects treated with wide-spectrum antibiotics, Minerva Med (ITALY) Dec 1989 80 (12) p1331-4 ; Giardiello FM; Hansen FC 3d; Lazenby AJ; Hellman DB; Milligan FD; Bayless TM; Yardley JH , Collagenous colitis in setting of nonsteroidal antiinflammatory drugs and antibiotics, Dig Dis Sci (UNITED STATES) Feb 1990 35 (2) p257-60; Skosyreva AM , Comparative evaluation of the embryotoxic effect of various antibiotics, Antibiot Khimioter (USSR) Oct 1989 34 (10) p779-82; Shields CB; Reid KH; Garretson HD; Byrd RP , Electrocortical and histopathologic effects of intrathecal antibiotics, Surg Forum (UNITED STATES) 1978 29 p495-7; Ng SC; Lee MK; Teh A , Acute organic brain syndrome due to drug-induced eosinophilia, Med J (ENGLAND) Nov 1989 65 (769) p843-4 ; Meijer-Severs GJ; Joshi JH , The effect of new broad-spectrum antibiotics on faecal flora of cancer patients, J Antimicrob Chemother (ENGLAND) Oct 1989 24 (4) p605-13; Manenti F; Ferrari A , Drug-induced liver diseases (editorial), G Clin Med (ITALY) Dec 1989 70 (12) p723-32; Effects of antibiotics on the gastrointestinal tract. Kunin CM Clin Pharmacol Ther (UNITED STATES) Jul-Aug 1967 8 (4) p495-501; Fillastre JP; Dhib M; Godin M; Moulin B , Drug-induced nephropathies, Ann Med Interne (Paris) (FRANCE) 1989 140 (7) p600-4; Pequignot H; Husson R , Drug-induced complications and professional responsibility, Ann Med Interne (Paris) (FRANCE) 1989 140 (7) p582-4; Hannig M; Hanpft R , Surveillance and assessment of undesirable effects in drug treatment: pilot project, Soz Praventivmed (SWITZERLAND) 1989 34 (6) p272-7 ; Anggelutsa PA; Brizinskii MA, Allergic complications in patients with rheumatism, Ter-Vartan'ian SKh Vrach Delo (USSR) Sep 1989 (9) p9-12 ; Hanpft R; Hannig M , Intensified risk monitoring of new drugs in general practice by the established physician, Verh Dtsch Ges Inn Med (GERMANY, WEST) 1989 95 p675-82; Lode H , Frequent errors in antibiotic therapy, Verh Dtsch Ges Inn Med (GERMANY, WEST) 1989 95 p400-3 ; Schollmeyer P , Urinary tract infections, antibiotics, Verh Dtsch Ges Inn Med (GERMANY, WEST) 1989 95 p260-2 ; When drug therapy causes diarrhea. RN (UNITED STATES) Dec 1989 52 (12) p32-5; Ligresti DJ , Anaphylaxis, Clin Dermatol (UNITED STATES) Jan-Mar 1986 4 (1) p40-9; Fellner MJ; Ledesma GN; Miller D , Adverse reactions to antibiotics other than penicillin, Clin Dermatol (UNITED STATES) Jan-Mar 1986 4 (1) p142-8 ; Murtaugh RJ; Mason GD , Antibiotic pressure and nosocomial disease, Vet Clin North Am Small Anim Pract (UNITED STATES) Nov 1989 19 (6) p1259- 74 ; Martino P; Micozzi A; Girmenia C; Raccah R; Gentile G , Fungal infections in the granulocytopenic patient, Haematologica (Pavia) (ITALY) Oct 1989 74 (5 Suppl) p320-31; Hetenyi G , Possible interactions between antibiotics and oral contraceptives, Ther Hung (HUNGARY) 1989 37 (2) p86-9; Brown RB; Levin J; Morris A , Adverse effects of antibiotics, J Am Podiatr Med Assoc (UNITED STATES) Oct 1989 79 (10) p500-4 ; McCluskey WP; Esterhai JL Jr; Brighton CT, Heppenstall RB, Neutropenia complicating parenteral antibiotic treatment of infected nonunion of the tibia, Arch Surg (UNITED STATES) Nov 1989 124 (11) p1309-12 ; Fleischer AB Jr; Resnick SD, The effect of antibiotics on the efficacy of oral contraceptives. A controversy revisited, Arch Dermatol (UNITED STATES) Nov 1989 125 (11) p1562-4 ; Oizumi K; Onuma K; Watanabe A; Motomiya M , Clinical study of drug fever induced by parenteral administration of antibiotics, Tohoku J Exp Med (JAPAN) Sep 1989 159 (1) p45-56 ; Hastie KJ; Weymont G; Lewis DA , An outbreak of Clostridium difficile associated diarrhoea in urological practice: a potential consequence of excessive antibiotic prophylaxis?, J R Coll Surg Edinb (ENGLAND) Jun 1989 34 (3) p146-8 ; Wey SB; Mori M; Pfaller MA; Woolson RF; Wenzel RP , Risk factors for hospital-acquired candidemia. A matched case-control study, Arch Intern Med (UNITED STATES) Oct 1989 149 (10) p2349-53 ; Zel'tser IZ, Prediction of dysbiotic effect in toxico-hygienic assessment of antibiotics, Antibiot Khimioter (USSR) Jun 1989 34 (6) p440-3 ; Vazquez de la Villa A; Luna del Castillo JD; Galdo Munoz G; Puche Canas E , Adverse reactions caused by drugs in pediatrics, An Esp Pediatr (SPAIN) Jul 1989 31 (1) p49-53; Samoilova LN; Tabakova TV; Popova NG , The clinical picture and diagnosis of drug allergy, Med Sestra (USSR) Jul 1989 48 (7) p27-31 ; Pallasch TJ , A critical appraisal of antibiotic prophylaxis, Int Dent J (ENGLAND) Sep 1989 39 (3) p183-96 ; Selby JV; Friedman GD; Fireman BH, Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up, Cancer Res (UNITED STATES) Oct 15 1989 49 (20) p5736-47; Topham JC; Murgatroyd LB; Jones DV; Goonetilleke UR; Wright J , Safety evaluation of meropenem in animals: studies on the kidney, J Antimicrob Chemother (ENGLAND) Sep 1989 24 Suppl A p287-306 ; Steele RW; Kearns GL , Antimicrobial therapy for pediatric patients, Pediatr Clin North Am (UNITED STATES) Oct 1989 36 (5) p1321-49 ;
3. Antimetabolics.
Folic acid antagonists:
3.1.METHOTREXAAT
Chemical denomination: 4-amino-N10-methyl-pteroyl-glutamic acid or A-methopterine. (NSC 740).
Action: co-enzym (préstage of enzym) folic acid plays an active role in the synthesis of purine, pirimidine and their nucleotides. Antifolic remedies have been created in cancer therapies.
In normal surroundings, folium acid is reduced to dihydrofolic acid and then to tetrahydrolofic acid. Thanks to their action on dihydrofolate-reductase, these folium antagonists prevent the transformation from dihydrofolic acid into tetrahydrofolic acid.
Brands: METHOTREXATE® (Rhône-Poulenc, Specia), LEDERTREXATE® (Lederle), ABITREXATE® (Abic), EMTHEXATE® (Pharmachemie), MEXATE® (Bristol-Myers), METHOTREXATUM® (INN), EMTEXATE® (Nordic), FARMITREXAT ® (Farmitalia), FARMOTREX® (Farmos), FOLEX® (Adria), MAXTREX® (Farmitalia), METOTREXATO® (Argentina), METREXAN® (Pharmacia), TREMETEX® (Laakefarmos).
Side effects:
3.2. Purine antagonists:
3.2.1. 6-MERCAPTOPURINE
Chemical denomination: purine-6-thiol monohydraat. (NSC 755).
Action: is a structural analogy of adenine and acts through inhibiting the transformation of the nucletode of hypoxantine (inosine acid or inosine-5'-monophosphate) in the nucleotides of xanthin and adenine. It also acts on the biosynthesis of purine on the conversion level of 5-phosphoribosyl-pyrophosphate in 5-phosphoribosylamide.
Brands: PURINETHOL® (Wellcome), MERCAPTOPURINUM® (INN), ISMIPUR® (ISM), PURI-NETHOL® (Wellcome, Calmic),
Side effects:
Sakamaki H; Nakamura S; Maruyama Y; Nagata K; Yahara Y; Onozawa Y, Chronic myelocytic leukemia following chemotherapy of acute promyelocytic leukemia, Rinsho Ketsueki (JAPAN) Nov 1989 30 (11) p1975-81 ; Hayder S; Lafolie P; Bjork O; Peterson C , 6-mercaptopurine plasma levels in children with acute lymphoblastic leukemia: relation to relapse risk and myelotoxicity, Ther Drug Monit (UNITED STATES) Nov 1989 11 (6) p617-22 ; Cappell MS; Das KM, Rapid development of pancreatitis following reuse of 6-mercaptopurine, J Clin Gastroenterol (UNITED STATES) Dec 1989 11 (6) p679-81; Present DH; Meltzer SJ; Krumholz MP; Wolke A; Korelitz BI, 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity, Ann Intern Med (UNITED STATES) Oct 15 1989 111 (8) p641-9 ;
3.2.2. 6-THIOGUANINE
Chemical denomination: 6-mercapto-2-amino-purine. (NSC 752).
Action: as purine antagonist who is - in contradiction to 6-Mercaptopurine - incorporated in the DNA and thus leads to an abnormal DNA.
Brands: THIOGUANINE®, LANVIS® (Wellcome, Calmic), THIOGUANINUM® (INN).
Side effects:
3.2.3.1. VIDARABINE (ARA-A)
Side effects:
Gizzi M; Rudolph S; Perakis A , Ocular flutter in vidarabine toxicity., Am J Ophthalmol (UNITED STATES) Jan 15 1990 109 (1) p105 ; Chen CW Kao Hsiung I , Adverse side effects caused by topically applied antiviral agents in herpetic keratitis, Hsueh Ko Hsueh Tsa Chih (TAIWAN) Aug 1989 5 (8) p416-29
3.2.3.2. CYTARABINE (ARA-C),
CYTOSINE ARABINOSIDE,
ARABINOSYL-CYTOSINE.Chemical denomination: 1-ß-D-arabino-furano-sylcytosine. (NSC 63878).
Brands: ALEXAN® (Mack, Pfizer), ARABITIN® (Japan), CYTOSAR® (Upjohn), ARACYTINE® (Upjohn), ERPALFA® (INTES), IRETIN® (Japan), UDICIL® (Upjohn), CYTARABINUM® (INN).
Side effects:
Drzewoski J; Krykowski E; Robak T; Jerzmanowski P; Kusowska J; KozbiaL H, Ventricular fibrillation in a patient with myelodysplastic syndrome treated with small doses of cytarabine, Kardiol Pol (POLAND) 1989 32 (4) p225-8 ; Andersson BS; Luna MA; Yee C; Hui KK; Keating MJ; McCredie K, Fatal pulmonary failure complicating high-dose cytosine arabinoside therapy in acute leukemia, Cancer (UNITED STATES) Mar 1 1990 65 (5) p1079-84; Malapert D; Degos JD, Painful legs and moving toes. Neuropathy caused by cytarabine, Rev Neurol (Paris) (FRANCE) 1989 145 (12) p869-71; Mahaney FX Jr, Physicians warned of high-dose cytarabine [news], J Natl Cancer Inst (UNITED STATES) Feb 21 1990 82 (4) p259-61 ; Sakamaki H; Nakamura S; Maruyama Y; Nagata K; Yahara Y; Onozawa Y, Chronic myelocytic leukemia following chemotherapy of acute promyelocytic leukemia, Rinsho Ketsueki (JAPAN) Nov 1989 30 (11) p1975-81; Tjon A Tham RT; Vlasveld LT; Willemze R, Gastrointestinal complications of cytosine-arabinoside chemotherapy: findings on plain abdominal radiographs, AJR Am J Roentgenol (UNITED STATES) Jan 1990 154 (1) p95-8; Sotiropoulos SV; Jackson MA; Woods GM; Hicks RA; Cullen J; Freeman AI , Alpha-streptococcal septicemia in leukemic children treated with continuous or large dosage intermittent cytosine arabinoside, Pediatr Infect Dis J (UNITED STATES) Nov 1989 8 (11) p755-8; Williams SF; Larson RA , Hypersensitivity reaction to high-dose cytarabine, Br J Haematol (ENGLAND) Oct 1989 73 (2) p274-5 ;
3.2.3.3. AZACITIDINE
Chemical denomination: 4-amino-1-ß-D-ribofuranosyl-1,3,5-triazine-2(1H)-one. (NSC 102816).
Brands: MYLOSAR® (Upjohn).
3.2.4. DIC
Chemical denomination: 5-(3,3-dimethyl-1-triazeno)-imidazol-4-carboxamide.
Action: as a structural analogy of 5-amino-imidazol-5-carboxamid, who is the precursor of the purine basis in their biosynthesis. Probably an alkylating effect on its metabolites, comparable with the related 5-(3,3-bis(2-chloroethyl)-1-triazeno)-imidazole-4-carboxamid.
Brands: not commercialized.
3.2.5. THIOINOSINE
Chemical denomination: 9-ß-D-ribofuranosyl-9H-purine-6-thiol.
Action: is a rubocid from mercaptopurine and has a similar effect.
Brands: THIOINOSIE® (Morishita, Japan).
3.2.6. AZATHIOPRINE
Chemical denomination: 6-(1-methyl-4-nitroimidazole-5-ylthio)purine. (NSC 39084).
Brands: AZAMUNE® (Penn), AZANIN® (Japan), AZAPRESS® (Lennon), IMURAN® (Wellcome), IMUREK® (Wellcome), IMUREL® (Wellcome), THIOPRINE® (Alphapharm).
3.3. Pyrimidine- and nucleic acid antagonists.
3.3.1.1. FLUOROURACIL
Chemical denomination: 5-fluor-1,2,3,4-tetrahydro-pyrimidine-2,4-dion. (NSC 19893).
Action: after the conversion into nucleotide, a twofold action : a). inhibiting of the DNA-synthesis by eliminating the thymidylate synthetase which causes a shortage in thymidine, and b). changes in the DNA where the remedy enters.
Brands: FLUORO-URACIL® (Roche, Hoffman-La Roche), EFUDIX® (Roche), FLUOROURACIL® (Abic), ADRUCIL® (Adria), ARUMEL® (Japan), CARZONAL® (Japan), EFFLUDERM® (Allergan), EFUDIX® (Roche), FLUOROPLEX® (Allergan, Herbert), FLUROBLASTIN® (Farmitalia), FLUROBLASTINE® (Farmitalia), TIMAZIN® (Japan), ULUP® (Japan).
Side effects:
Blackburn WD Jr; Alarcon GS, Toxic response to topical fluorouracil in two rheumatoid arthritis patients receiving low-dose, weekly methotrexate [letter], Arthritis Rheum (UNITED STATES) Feb 1990 33 (2) p303-4 ; Murin J; Kasper J; Danko J; Cerna M; Bulas J; Uhliar R , The development of myocardial infarct in a patient treated with 5- fluorouracil, Vnitr Lek (CZECHOSLOVAKIA) Oct 1989 35 (10) p1020-4; Kuzel T; Esparaz B; Green D; Kies M, Thrombogenicity of intravenous 5-fluorouracil alone or in combination with cisplatin, Cancer (UNITED STATES) Feb 15 1990 65 (4) p885-9; Moore DH; Fowler WC Jr; Crumpler LS , 5-Fluorouracil neurotoxicity, Gynecol Oncol (UNITED STATES) Jan 1990 36 (1) p152-4; Mazoyer G; Assouline D; Fourchard V; Kalb JC , Cardiotoxicity of 5 fluoro-uracil, Rev Mal Respir (FRANCE) 1989 6 (6) p551-3; Wadler S; Lyver A; Wiernik PH , Clinical toxicities of the combination of 5-fluorouracil and recombinant interferon alfa-2a: an unusual toxicity profile, Oncol Nurs Forum (UNITED STATES) Nov-Dec 1989 16 (6 Suppl) p12-5 ; Curran CF; Luce JK, Fluorouracil and palmar-plantar erythrodysesthesia [letter], Ann Intern Med (UNITED STATES) Nov 15 1989 111 (10) p858; Dozono H; Nakamura K; Motoya T; Nakamura S; Shinmura R; Miwa K; Ishibashi M; Nagata Y, Prevention of stomatitis induced by anti-cancer drugs, Gan To Kagaku Ryoho (JAPAN) Oct 1989 16 (10) p3449-51 ; Besnard V; Leroy B; Vilette B; Scherpereel P , Cardiomyopathy due to 5-fluorouracil, Cah Anesthesiol (FRANCE) Jun-Jul 1989 37 (4) p299-301;
3.3.1.2. TEGAFUR
Chemical denomination: 5-fluoro-1-(tetrahydro-2-furyl)uracil. (NSC 148958).
Action: through secretion of fluorouracil in the body.
Brands: CITOFUR® (Lusofarmaco), COPAROGIN® (Japan), EXONAL® (Japan), FENTAL® (Japan), FH® (Japan), FRANROZE® (Japan), FULAID® (Japan), FULFEEL® (Japan), FULTOL-P® (Japan), FURAFULUOR® (Japan), FUROFUTRAN® (Japan), FUTRAFUL® (Japan), HELPA® (Japan), ICALUS® (Japan), LAMAR® (Japan), LIFRIL® (Japan), LUNACIN® (Japan), NEBERK® (Japan), NITOBANIL® (Japan), PHARMIC® (Japan), RICHINA® (Japan), RIOL® (Japan), SINOFLUROL® (Japan), TEFSIEL-C® (Japan), TORAFURINE® (Morrith), UTEFOS® (Almirall).
3.3.1.3. FLOXURIDINE
Chemical denomination: 1-(2-deoxy-ß-D-ribofuranosyl)-5-fluoropyrimidine-2,4(1H,3H)-dione. (NSC 27640).
Action: like fluorouracil.
Brands: not commerciallized (Roche).
3.3.2. 6-AZAURACIL
Chemical denomination: 6-azauracil riboside. (NSC 32074).
Action: like antimetabolite.
Brands: not commercialized.
3.3.3. 6-AZAURIDINE
Chemical denomination: 6-azauridine. (NSC 32974).
Action: like antimetabolite.
Brands: not commercialized.
3.3.4. 3-DEAZAURIDINE
Chemical denomination:
Action:
Brands:
3.3.5. 5-AZACYTIDINE
Chemical denomination: 4-amino-1-ß-D-ribofuraosyl. (NSC 102816).
Action: like cytarabine.
Brands: MYLOSAR® (Upjohn).
3.4. Glutamine antagonists
3.4.1. AZASERINE
Chemical denomination:
Action:
Brands: no clinical application any more.
3.4.2. DIAZO-OXO-NORLEUCINE
or D.O.N.Chemical denomination:
Action:
Brands: no clinical application any more.
3.5. CYTEMBENA
Chemical denomination:
Action:
Brands:
4. Vegetal alkaloids.
Action: these alkaloids from plants have an antimitotic capacity, which means that by means of poison they influence the cell division. In high concentrations these substances also influence the nucleic acid- and protein synthesis.
Side effects:
Chambers SK; Flynn SD; Del Prete SA; Chambers JT; Schwartz PE , Bleomycin, vincristine, mitomycin C, and cis-platinum in gynecologic squamous cell carcinomas: a high incidence of pulmonary toxicity, Gynecol Oncol (UNITED STATES) Mar 1989 32 (3) p303-9; VanDemark RE Sr , Colchicine [editorial] , S D J Med Sep 1988 41 (9) p13; MacLeod PM; Tyrrell CJ; Bliss B , Raynaud's phenomenon following cytotoxic chemotherapy successfully managed by dorsal sympathectomy, Eur J Surg Oncol (ENGLAND) Feb 1989 15 (1) p79-81; Gordon AN; Lynch GR , Multi-agent chemotherapy in combination with fractioned radiation therapy for advanced carcinoma of the cervix: acute toxicity, Eur J Gynaecol Oncol 1988 9 (5) p351-4 ; Siddall SJ; Martin J; Nunn AJ , Anaphylactic reactions to teniposide [letter] , Lancet (ENGLAND) Feb 18 1989 1 (8634) p394 ; Kanoh T , Fatal paralytic ileus following vindesine chemotherapy in a patient with myeloma-associated amyloidosis [letter], Eur J Haematol (NETHERLANDS) Jan 1989 42 (1) p108 ; Viens P; Lagrange JL; Thyss A; Ayela P; Frenay M; Schneider M, Brain metastases of lung cancer: excessive toxicity of high dose VP 16 213 [letter], Eur J Cancer Clin Oncol (ENGLAND) Dec 1988 24 (12) p1905-6; Afanas'ev VN; Korol' BA; Matylevich NP; Pechatnikov VA; Umanskii SR , The patterns of colchicine-induced death of lymphoid cells, Tsitologiia Sep 1988 30 (9) p1108-16; Wiktor-Jedrzejczak W; Siekierzynski M; Rychowiecka E; Bukowska B; Czarnecki C , Changes in peripheral blood composition following single and repeated courses of intermittent cancer chemotherapy, Med Interne Oct-Dec 1982 20 (4) p289-94; Chong CD; Logothetis CJ; Savaraj N; Fritsche HA; Gietner AM; Samuels ML , The correlation of vinblastine pharmacokinetics to toxicity in testicular cancer patients, J Clin Pharmacol (UNITED STATES) Aug 1988 28 (8) p714-8 ; Love RR; Leventhal H; Easterling DV; Nerenz DR, Side effects and emotional distress during cancer chemotherapy, Cancer Feb 1 1989 63 (3) p604-12; Indiano JM; Gonzalez A; Oria de Rueda O; Sanchez E , Inappropriate ADH syndrome and other toxic effects in the course of childhood ALL treated with vincristine, An Esp Pediatr (SPAIN) Oct 1988 29 Suppl 34 p155-6; Cerny T; Pedrazzini A; Joss RA; Brunner KW , Unexpected high toxicity in a phase II study of teniposide (VM-26) in elderly patients with untreated small cell lung cancer (SCLC), Eur J Cancer Clin Oncol (ENGLAND) Nov 1988 24 (11) p1791-4; Steurer G; Kuzmits R; Pavelka M; Sinzinger H; Fritz E; Ludwig H, Early-onset thrombocytopenia during combination chemotherapy in testicular cancer is induced by vinblastine, Cancer (UNITED STATES) Jan 1 1989 63 (1) p51-8 ; Gupta R, Tests for the genotoxicity of m-AMSA, etoposide, teniposide and ellipticine in Neurospora crassa, Mutat Res (NETHERLANDS) Feb 1990 240 (2) p47-58; Gardner G; Mesler D; Gitelman HJ, Hemolytic uremic syndrome following cisplatin, bleomycin, and vincristine chemotherapy: a report of a case and a review of the literature, Chapel Hill. Ren Fail (UNITED STATES) 1989 11 (2-3) p133-7; Di Gregorio F; Favaro G; Fiori MG , Functional evaluation of acute vincristine toxicity in rat skeletal muscle, Muscle Nerve (UNITED STATES) Dec 1989 12 (12) p1017-23 ; Carneiro PC; Pereira ED; Mitteldorf CS; Martinez GA; Beitler B; Pozzi DH , Acute myeloid leukemia after treatment of Hodgkin's disease], Rev Hosp Clin Fac Med Sao Paulo (BRAZIL) Mar-Apr 1989 44 (2) p87-90; Chauffert B; Lorcerie B; Andre F; Besancenot JF; Martin F , Recurrent paralysis induced by vincristine during the treatment of Hodgkin's disease (letter), Presse Med (FRANCE) Nov 25 1989 18 (39) p1930-1; McGuire SA; Gospe SM Jr; Dahl G , Acute vincristine neurotoxicity in the presence of hereditary motor and sensory neuropathy type I, Med Pediatr Oncol (UNITED STATES) 1989 17 (6) p520-3 ; Lahtinen R; Koponen A; Mustonen J; Soppi E; Lansimies E; Nousiainen T; Lahtinen R , Discordance in the development of peripheral and autonomic neuropathy during vincristine therapy [letter], Eur J Haematol (NETHERLANDS) Oct 1989 43 (4) p357-8; Heran F; Defer G; Brugieres P; Brenot F; Gaston A; Degos JD , Cortical blindness during chemotherapy: clinical, CT, and MR correlations., J Comput Assist Tomogr (UNITED STATES) Mar-Apr 1990 14 (2) p262-6
4.1. VINCRISTINE SULPHATE (VCR),
LEUROCRISTINEOrigin: alkaloids from vinca rosea, catharantus roseus. (NSC 67574).
Brands: ONCOVIN® (Lilly), VINCRISTINESULFAAT® (Abic, Lederle, Cyanamid), VINCRISTINI SULFAS® (Pharmachemie), VINCRISTINUM® (INN), KYOCRISTINE® (Japan), PERICRISTINE® (Z.-Afrika), VINCASAR® (Adria), VINCRISUL® (Lilly)..
4.2. VINBLASTINE SULPHATE (VLB),
VINCALEUCOBLASTINEOrigin: alkaloids from vinca rosea, catharantus roseus. (NSC 49842).
Brands: VELBE® (Lilly), VINBLASTINE-SULFAAT® (Lederle, Cyanamid), VINBLASTINUM® (INN), VELBAN® (Lilly).
4.3. VINDESINE SULPHATE
Origin: semi-synthetic derivation of vinblastine.
Brands: ELDISINE® (Lilly), ENISON® (Lilly).
4.4. VINGLYCINATE
4.5. VINLEUROSINE
4.6. VINROSIDINE
4.7. VINZOLIDINE SULPHATE
Clan: structurel related to vinblastine.
Brands: not commercialized (Lilly).
4.8. Epipodophyllotoxins.
4.8.1. TENIPOSIDE (VM 26)
Chemical denomination: 4'-demethyl-9-4,6-0-2-thenilidene-ß-D-glucopyranoside. (NSC 122819).
Brands: VUMON® (Bristol-Myers), TENOPOSIDUM® (INN), VEHEM® (Sandoz).
4.8.2. VP 16 213 (EPE), ETOPOSIDE
Chemical denomination: 4'-demethyl-9-4,6-0-2-ethylideen-ß-D-glucoside. (NSC 141540).
Brands: not commercialized (SANDOZ), VEPESID® (Bristol-Myers), ETOPOSIDUM® (INN), ETOPOL® (Joegosl.).
4.8.3. PODOPHYLINEDERIVATE
4.9. COLCHICINE
Side effects:
Urtizberea M; Bourre JM; Debray M; Scherrmann JM, Comparison of colchicine toxicity on different dysmyelinating mutant models, Neurotoxicology (UNITED STATES) Summer 1989 10 (2) p211-7 ; Dudin A; Rambaud-Cousson A; Shehatto M; Thalji A , Colchicine in the first trimester of pregnancy and vertebral malformations Arch Fr Pediatr (FRANCE) Oct 1989 46 (8) p627-8;
5. Cytotoxic substances with various structure and acting mechanisms.
5.1. L-ASPARAGINASE, COLASPASE
Clan: Substracted from escherichia coli or erwinia carotova or from other germs.
Action: cataliyses the hydrolysis of L-asparagine in L-aspartic acid and ammonium, which causes a shortage of asparagine, which slows down the synthesis of proteins. Only cells short of asparagine synthetase (as some leucemia cells) are sensitive to L-asparaginase.
Brands: KIDROLASE® (Rhône-Poulenc, Bellon), CRASNITIN® (Bayer), CRASNITINE® (Bayer), ELSPAR® (Merck, Sharp & Dohme), ERWINASE® (Porton), LASPAR® (MPS Lab.), LEUCOGEN® (Bayer), LEUNASE® (May & Baker).
5.2. HYDROXYUREA,
HYDROXYCARBAMIDEChemical denomination: 1-hydroxy-urea. (NSC 32065).
Action: impairment of the biosynthesis of nucleic acids by influencing the ribonucleoside diphosphate reductase.
Brands: HYDREA® (Squibb), HYDROXYCARBAMIDUM® (INN), LITALIR® (Rhône-Poulenc), ONCO-CARBIDE® (Simes).
5.3. MITOGUAZONE
Chemical denomination: 1,1-{(methylethanediylidene) dinitrolo} diguanidine. (NSC 32946).
Brands: not commercialized (Riom).
5.4. RAZOXANE
Chemical denomination: (+/-)-4,4'-propylene-bis(piperazine-2,6-dione). (NSC 129943).
Brands: RAZOXIN® (ICI Pharm).
5.5. Nitrosol preparations.
5.5.1. CARMUSTINE (BCNU)
Chemical denomination: 1,3-bis(2-chloroethyl)1-nitroso urea. (NSC 409962).
Action: by inhibiting the purinesynthesis.
Brands: CARMUBRIS® (Bristol), BECENUM® (Bristol-Myers), BiCNU® (Bristol), NITRUMON® (Simes), CARMUSTINUM® (INN).
5.5.2. LOMUSTINE (CCNU)
Chemical denomination: 1-(2-chloroethyl)-3-cyclohexyl-1 nitroso urea. (NSC 79037).
Action: by inhibiting the purinesynthesis.
Brands: LUCOSTINE® (Lundbeck), CECENU® (Bellon), CCNU® (Rhône-Poulenc, Lundbeck, Abic), BELLUSTINE® (Bellon), CeeNU® (Bristol-Myers), CiNU® (Bristol), LOMUSTINUM® (INN).
5.5.3. METHYL-CCNU, SEMUSTINE
Chemical denomination: 1-(2-chloroethyl)-3-(4-Methylcyclo-hexyl)-1-nitroso urea. (NSC 95441).
Brands: not commercialized (National Institutes of Health, USA).
5.5.4. STREPTOZOCINE
Chemical denomination: 2-deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose. (NSC 85998).
Brands: ZANOSAR® (Upjohn).
5.5.5. NIMUSTINE
Chemical denomination: 3-{(4-amino-2-methyl-5-pyrimidinyl)-methyl}-1-(2-chloroethyl)-1-nitroso-urea. (NSC 245382).
Brands: ACNU 50® (Asta), NIDRAN® (Sankyo), NIMUSTINUM® (INN).
5.5.6. MUSTINE
Chemical denomination: NN-bis(2-chloroethyl)-methylamine hydrochloride. (NSC 762).
Action: by alkylation
Brands: CARYOLYSINE® (Delagrange), CLORAMIN® (Italiè), ERASOL® (Denem.), MUSTARGEN® (Merck, Sharp & Dohme).
5.5.7. URAMUSTINE
Chemical denomination: 5-bis-(2-chloroethyl)-aminouracil. (NSC 34462).
Action: derived from mustine with one and the same effect.
Brands: not commercialized (Upjohn).
5.6. PIPOBROMAAN
Chemical denomination: 1,4-bis (3-bromoproprionyl) piperazine. (NSC 25154).
Action: probably by alkylation.
Brands: VERCYTE® (Abbott), AMEDEL® (Japan), VERCITE® (Abbott), PIPOBROMANUM® (INN).
5.7. PIPOSULPHANE
Chemical denomination: N,N-bis-(3-methaan-sulfonoxy-propanoyl) piperazine.
Action: probably by alkylation.
Brands: ANCYTE® (Abbott).
5.8. DIBROMOMANNITOL
Chemical denomination: 1,6-dibromo-1,6-didesoxy-D-mannitol.
Action: probably by alkylation.
Brands: MYELOBROMOL®
5.9. ESTRAMUCINE
Chemical denomination: estra-1,3,5,(10)-triene-3,17ß-diol 3-[bis(2-chloroethyl)carbamaat] 17-(disodium-fosfaat). (NSC 89199).
Action: like mustine.
Brands: EMCYT® (Roche), ESTRACYT® (Lundbeck, roche, Pharmacia Arzneimittel, Mekos, MPS Labo, Abello, Leo).
5.10. ETHOGLUCID
Chemical denomination: 1,2:15,16-diepoxy-4,7,10,13-tetraoxahexadecaan.
Action: by alkylation.
Brands: EPODYL® (ICI).
Side effects of nitrosol preparations:
Sen P; Bailey NM; Hagemeister FB; Liang JC, Induction of chromosome breaks and sister chromatid exchanges in patients with Hodgkin's disease by two combination chemotherapy regimens of different leukemogenic potential, Cancer Res (UNITED STATES) Feb 1 1990 50 (3) p558-62 ; Rosenblum MK; Delattre JY; Walker RW; Shapiro WR , Fatal necrotizing encephalopathy complicating treatment of malignant gliomas with intra-arterial BCNU and irradiation: a pathological study, J Neurooncol (UNITED STATES) Sep 1989 7 (3) p269-81 ; van den Anker-Lugtenburg PJ; Sizoo W , Myelodysplastic syndrome and secondary acute leukemia after treatment of essential thrombocythemia with hydroxyurea [letter], Am J Hematol (UNITED STATES) Feb 1990 33 (2) p152; Richard M; Truchetet F; Friedel J; Leclech C; Heid E , Skin lesions simulating chronic dermatomyositis during long-term hydroxyurea therapy, Am Acad Dermatol (UNITED STATES) Oct 1989 21 (4 Pt 1) p797-9 ; Zucker PF; Archer MC , Streptozotocin toxicity to cultured pancreatic islets of the Syrian hamster, Cell Biol Toxicol (UNITED STATES) Sep 1988 4 (3) p349-56 ; Somova L; Dashev G; Doncheva M; Vasileva M , Streptozotocin-induced non-insulin dependent diabetes mellitus in rats], Eksp Med Morfol (BULGARIA) 1988 27 (3) p9-17
6. Varia
6.1. MITOBRONITOL
Chemical denomination: 1,6-dibromo-1,6-dideoxy-D-mannitol. (NSC 94100).
Brands: MYEBROL® (Japan), MYELOBROMOL® (Sinclair).
6.2. MITOCLOMINE
Chemical denomination: 4-amino-N-N bis (chloroethyl)-1-methoxy-2-methyl-naphtalene.
Brands: not commercialized.
6.3. MITOCROMINE
6.4. MITOGILLINE
6.5. MITOLACTOL
Chemical denomination: 1,6-dibromo-1,6-dideoxy-D-galactitol. (NSC 104800).
Brands: ELOBROMOL® (Chinoin, Hungary).
6.6. MITOMALCINE
6.7. MITOPODOZINE
6.8. QUINACRINE
Chemical denomination: 3-chloro-7-methoxy-9-(1-methyl-1-4-diethylamino-butylamino) acridine
Brands: QUINACRINE®, ATEBRINE®.
6.9. 6-AMINOCHRYSENE
Chemical denomination: 6-aminochrysene.
Brands: CHRYSENEX®
6.10. ALTRETAMINE
Chemical denomination: 2,4,6-tris(dimethylamino)-1,3,5-triazine.
Action: not completely known: the remedy itself is inactive though the metabolites could have an alkylating effect.
Brands: HEXASTAT® (Bellon), ALTRETAMINUM® (INN).
6.11. AMSACRINE
Chemical denomination: 4'-(9-acridinylamino)-methanesulfon-m-anisidide. (NSC 249992).
Action: by inhibiting the DNA synthesis.
Brands: AMSIDINE® (Parke-Davis), AMEKRIN® (Parke-Davis), AMSA® (Parke-Davis), AMSIDYL® (Parke-Davis, Gödecke), AMSACRINUM® (INN).
7. Hormones and anti-hormones.
Action:
Generally, hormone therapy in cancers takes account of the fact that hormones control the growth of certain organs, who have shown to be physiological dependant on these hormones. Hormones are therapeutically used in goal- and organ oriented therapies on cancer in organs who keep on prooving their hormonal relationship.
Steroid-hormones.
7.1. PREDNISONE
Chemical denomination: Delta-1-cortisone.
Brands: CORTANCYL®, DELTA-CORTISONE®, DI-ADRESON®.
7.2. PREDNISOLONE
Chemical denomination: Delta-hydrocortisone.
Brands: HYDROCORTANCYL®, DI-ADRESON-F®, DELTACORTRIL®, DI-ADRESON-F AQUOSUM®, SOLU-DACORTINE®.
7.3. METHYLPREDNISOLONE
Chemical denomination: methylprednisolone
Brands: MEDROL®, DEPO-MEDROL®, SOLU-MEDROL®.
7.4. TRIAMCINOLONE
Chemiche benaming: 16-a-hydroxy-9 a-fluoro-predni-solone.
Brands: KENACORT®, TEDAROL®, LEDERCORT®, ALBICORT®.
7.5. DEXAMETHASONE
Chemical denomination: 16-a-methyl-9 a-fluoro-prednisolone.
Brands: DERONIL®, ORADEXON®, DECADRON®, DECTANCYL®, DEXA-CORTANCYL®, ORADEXON®.
7.6. BETAMETHASONE
Chemical denomination: 16-ß-methyl-9 a-fluoro-prednisolone.
Brands: BETNESOL®, CELESTENE®, CELESTONE®, BETNELAN®.
7.7. PARAMETHASONE
Chemical denomination: 16-a-methyl-6 a-fluoro-prednisolone.
Brands: DILAR®.
Androgene-hormones.
7.8. TESTOSTERONEPROPRIONATE
Chemical denomination: testosteroneproprionate.
Brands: TESTOVIRON®.
7.9. TESTOSTERONEŒNANTHATE
Chemical denomination: testosterone-œnanthate.
Brands: ANDROTARDYL®, TESTOVIRON-DEPOT®.
7.10. FLUOXYMESTERONE
Chemical denomination: 9-a-fluoro-11-ß-hydroxy-17- a-methyltesterone.
Brands: HALOTESTIN®, ULTANDRENE®.
7.11. DROSTANALONEPROPRIONATE
Chemical denomination: androstanolone 4,5 a-dihydro-2 a-methyltestosterone.
Brands: PERMASTRIL®, MASTERON®.
7.12. DELTA-1-TESTOLOLACTONE
Chemical denomination: 17-a-oxa-D-homoandrosta-1,4-dienE-3,17-dione.
Brands: TESLAC®.
7.13. CALUSTERONE
Chemical denomination: 7 ß, 17-dimethyltestosterone.
Brands: not commercialized.
Œstrogene-hormones.
7.14. DIETHYLSTILBŒSTROL (DES)
Chemical denomination: diethylstibœstrol
Brands: DISTILBENE®.
7.15. DIHYDRO-DIFENYL-HEXADIENE-
DIENŒSTROLChemical denomination: dihydro-diphenyl-hexadiene-dienœstrol
Brands: CYCLADIENE®.
7.16. CHLOROTRIANISENE
Chemical denomination: tri-para-methoxyphenyl-chloro-ethylene.
Brands: TACE-FN®.
7.17 ETHYNILŒSTRADIOL
Chemical denomination: ethynilœstradiol.
Brands: ETHINYL-ŒSTRADIOL®, ETINŒSTRYL®, LYNORAL®.
7.18. TAMOXIFEN
Chemical denomination: (Z)-2-[4-(1,2-difenylbut-l-enyl)fenoxyl]-NN-dimethylethilaminecitrate.
Brands: ISTUBOL® (Chile), KESSAR® (Farmitalia); NOLTAM® (Lederle), NOLVADEX® (ICI), TAMAXIN® (Farmos, Laakefarmos), TAMOFEN® (Rhône-Poulenc), TAMOXASTA® (Asta), ZITAZONIUM® (Hongarije).
Progesterone-hormones.
7.19. PRO
Chemical denomination: 17 a-hydroxyprogesterone caproate.
Brands: PROGESTERONE-RETARD®, PROLUTON-DEPOT®.
7.20. MEDROXYPROGESTERONE
Chemical denomination: 17 a-hydroxy-6 a-methyl-progesterone.
Brands: PROVERA®, FARLUTAL®, DEPO-PROVERA®, FARLUTAL-DEPOT®.
7.21. CHLOORMADINONE
Chemical denomination: 6-chloor-6-dehydro-17 a-hydroxy-progesterone.
Brands: LUTERAN®.
7.22. MEGESTROL
Chemical denomination: 6-methyl-6-dehydro-17 a-acetoxy-progesterone.
Brands: NIAGESTINE®.
7.23. NORETHINDRONE
Chemical denomination: 17 a-ethynil-19-testosterone-acetate.
Brands: NORLUTEN®, FORFOR®, PRIMOLUT NOR®.
Thyroid-hormones.
7.24. LIOTHYRONINE
Chemical denomination: L-tri-iodo-thyronine.
Brands: CYNOMEL®, CYTOMEL®.
Cancer-producing side effects of the hormone-therapy:
Aldinger, K., Ben-Menachem, Y., Whalenm G.: Focal nodular hyperplasia of the liver associated with high-dosage estrogens, Arch. Intern. Med. 137, 357-359, 1977; Ameriks, J. A., Thompson, N. W., Frey, C. F., Appelman, H. D., Walter, J. F.: Hepatic cell adenomas, spontaneous liver rupture, and oral contraceptives, Arch. Surg. 110, 548-556, 1975; Andersen, P. H., Packer, J. T.: Hepatic adenoma, Observations after estrogen withdrawal, Arch. Surg. 111, 898-900, 1976; Anthony, P. P.: Hepatoma associated with androgenic steroids, Lancet 1, 685-686, 1975; Antoniades, K., Campbell, W. N., Hecksher, R. H., Kessler, W. B., McCarthy, G. E., Jr.: Liver cell adenoma and oral contraceptives, Double tumor development, JAMA 234, 628-629, 1975; Beaconsfield, P.: Liver tumours and steroid hormones, Lancet 1, 516-517, 1974; Begg, C. F., Berry, W. H.: Isolated nodules of regenerative hyperplasia of the liver, Am. J. Clin. Pathol. 27, 447-463, 1953; Berg, J. W., Ketelaar, R. J., Rose, E. F., Vernon R. G.: Hepatomas and oral contraceptives, Lancet 2, 349-350, 1974; Bernstein, W., Hunter, R. L., Yachnin, S.: Hepatoma and peliosis hepatis developing in a patient with Fanconi's anemia, New Engl. J. Med. 284, 1135-1136, 1971; Blendis, L. M., Parkinson, M. C., Shilkin, K. B., Williams, R.: Nodular regenerative hyperplasia of the liver in Felty's syndrome, Q. J. Med. 169, 25-32, 1974; Brander, W. L., Bewick, M., Ogg, C.: Liver hamartomas in patients on oral contraceptives, Br. Med. J. 2, 80, 1974; Brander, W. L., Vosnides, G., Ogg, C. S., West, I. E.: Multiply hepatocellular tumours in a patient treated with oral contraceptives, Virchows Arch. 370, 69-76, 1976; Bruguera, M.: Hepatoma associated with androgenic steroids, Lancet 1, 1295, 1975; Catalano, P. W., Early, M. E., Topoloshy, H. W., Martin, E. W., Jr., Carey, L. C.: Focal nodular hyperplasia of the liver, Report of six patients, Concepts of surgical management, Cancer 39, 587-591, 1977; Cattan, D., Vesin, P., Wautier, J., Khalifat, R., Meignan, S.: Liver tumours and steroid hormones, Lancet 1, 878, 1974; Christopherson, W. M., Mays, E. T.: Liver tumors and contraceptive steroids, Experience with one hundred registry patients, J. Natl. Cancer Inst. 58, 167-171, 1977; Christopherson, W. M., Mays, E. T., Barrows, G. H.: Liver tumors in women on contraceptive steroids, Obstet. Gynecol. 48, 221-223, 1975; Christopherson, W. M., Mays, E. T., Barrows, G.: A clinicopathologic study of steroid-related tumors, Am. J. Surg. PAthol. 1, 31-41, 1977; Cornish, P. G.: Liver cell adenoma, JAMA 235, 249, 1976; Davies, J. N. P.: Livers tumours and steroid hormones, Lancet 1, 516, 1974; Davis, M., Postmann, B., Searle, M., Wright, R., Williams, R.: Histological evidence of carcinoma in a hepatic tumour associated with oral contraceptives, Br. Med. 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H.: Oral contraceptive and malignant hepatoma, Lancet 1, 479, 1976; Goldfarb, S.: Sex hormones and hepatic neoplasia, Cancer Res. 36, 2584-2588, 1976; Guy, J. T., Auslander, M. O.: Androgenic steroids and hepatocellular carcinoma, Lancet 1, 148, 1973; Henderson, B. E., Benton, B., Edmondson, H. A.: Hepatocellular carcinoma and oral contraceptives, JAMA 236, 560, 1976; Henderson, J. T., Richmond, J., Sumerling, M. D.: Androgenic-anabolic steroid therapy and hepatocellular carcinoma, Lancet 1, 934, 1973; Holder, L. E., Gnarra, D. J., Lampkin, B. C., Nishiyama, H., Perkins, P.: Hepatoma associated with anabolic steroid therapy, Am. J. Roentgenol. 124, 638-642, 1975; Jhingran, A. K., Mukhopadhyay, A. K., Ajmani, S. K., Johnson, P. C.: Hepatic adenomas and focal hyperplasia of the liver in young women on oral contraceptives, Case reports. J. Nucl. Med. 18, 263-266, 1977; Johnson, F. L.: Androgenic-anabolic steroids and hepatocellular carcinoma, In: Hepatocellular Carcinoma. Okuda, K., Peters, R. L. (eds.), New York: John Wiley and Sons, 1976, pp. 95-103; Johnson, F. L., Feagler, J. R., Lerner, K. G., Majerus, P. W., Siegel, M., Hartmann, J. R., Thomas, E. D.: Association of androgenic-anabolic steroid therapy with development of hepatocellular carcinoma, Lancet 2, 1273-1276, 1972; Kay, C. R.: Oral contraceptives and liver tumours, Lancet 2, 127, 1975; Kew, M. C., Van Coller, B., Prowse, C. M., Skikne, B., Wolfsdorf, J. I., Isdale, J., Krawitz, S., Altman, H., Levin, S. E., Bothwell, T. H.: Occurence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids, S. Afr. Med. J. 50, 1233-1237, 1976; Klatskin, G.: Hepatic tumors, Possible relationship to use of oral contraceptives, Gastroenterology 73, 386-394, 1977; Knapp, W. A., Ruebner, B. H.: Hepatomas and oral contraceptives, Lancet 1, 270-271, 1974; Knowles, D. M., Wolff, M.: Focal nodular hyperplasia of the liver, A clinicopathologic study and review of the literature, Hum. Pathol. 7, 533-545, 1976; Knowles, D. M., Kaye, G. I., Godman, G. C.: Nodular regenerative hyperplasia of the liver, Gastroenterology 69, 746-751, 1975; Lesna, M., Spencer, I., Wolker, W.: Liver nodules and androgens, Lancet 1, 1124, 1976; Lingeman, C. H.: Evaluating carcinogenicity of oral contraceptives, JAMA 236, 1690, 1976; Mays, E.T.: Hepatocellular carcinoma and oral contraceptives, JAMA 236, 560, 1976; Mays, E. T., Christipherson, W. H., Barrows, G. H.: Focal nodular hyperplasia of the liver, Possible relationship to oral contraceptives, Am. J. Clin. Pathol. 61, 735-746, 1974; Mays, E. T., Christopherson, W. M., Mahr, M. M., Williams, H. C.: Hepatic changes in young women ingesting contrceptive steroids: hepatic hemorrhage and primary hepatic tumors, JAMA 235, 730-732, 1976; McKinney, G. R., Weikel, J. H., Jr., Webb, W. K., Dick, R. G.: Use of the life-table technique to estimate effects of certain steroids on probability of tumour formation in a long-term study in rats, Toxicol. Appl. Pharmacol. 12, 68-79, 1968; Meadows, A. T., Naiman, J. L., Valdes-Dapena, M.: Hepatoma associated with androgen therapy for aplastic anemia, J. Pediatr. 84, 108-110, 1974; Meyer, P., Livolsi, V. A., Cornog, J. L.: Hepatoblastoma associated with an oral contraceptive, Lancet 2, 1387, 1974; Model, D. G., Fox, J. A., Jones, R. W.: Multiple hepatic adenomas associated with an oral contraceptive, Lancet 1, 865, 1975; Mokrohisky, S. T., Ambruso, D. R., Hathaway, W. E.: Fulminant hepatic neoplasia after androgen therapy, New Engl. J. Med. 296, 1411-1412, 1977; Morton, R. F., Hebel, J. R.: Liver-cell adenomas and oral contraceptives, New Engl. J. Med. 295, 52, 1976; Mulvihill, J. J., Ridolfi, R. L., Schultz, F. R., Borzy, M. S., Haughton, P. B. T.: Hepatic adenoma in Fanconi anemia treated with oxymetholone, J. Pediatr. 87, 122-124, 1975; Nadell, J., Kosek, J.: Peliosis hepatis, Twelve cases associated with oral androgen therapy, Arch. Pathol. Lab. Med. 101, 405-410, 1977; Nissen, E. D., Kent, D. R.: Liver tumors and oral contraceptives, Obstet. Gynecol. 46, 460-467, 1975; Oral Contraceptives and Health, An Interim Report from the Oral Contraception Study of the Royal College of General Practitioners, New York: Pitman Publishing Corporation, 1974, pp. 1-100; Osterholzer, H. O., Grillo, D., Kruger, P. S., Dunnihoo, D. R.: The effect of oral contraceptive steroids on branches of the uterine artery, Obstet. Gynecol. 49, 227-232, 1977; O'Sullivan, J. P.: Oral contraceptives and liver tumors, Proc. R. Soc. Med. 69, 351-353, 1976; O'Sullivan, J. P., Rosswick, R. P.: Oral contraceptives and malignant hepatic tumors, Lancet 1, 1124-1125, 1976; O'Sullivan, J. P., Wilding, R. P.: Liver hamartomas in patients on oral contraceptives, Br. Med. J. 2, 7-10, 1974; Pryor, A. G., Cohen, R. J., Goldman, R. L.: Hepatocellular carcinoma in a women on long-term oral contraceptives, Cancer 40, 884-888, 1977; Sale, G. E., Lerner, K. G.: Multiple tumores after androgen therapy, Arch. PAthol. Lab. Med. 101, 600-603, 1977; Stauffer, J. Q., Hill, R. B.: Systemic contraceptives and liver tumors, Ann. Intern. Med. 85, 122-123, 1976; Thalassinos, N. C., Lymberatos, C., Hadjioannou, J., Gardikas, C.: Liver-cell carcinoma after long term oestrogen-like drugs, Lancet 1, 270, 1974; Tigano, F., Ferlazzo, B., Barrile, A.: Oral contraceptives and malignant hepatoma, Lancet 2, 196, 1976; Tyrer, L. B.: Liver-cell adenomas and oral contraceptives, New Engl. J. Med. 295, 51-52, 1976; Ziegenfuss, J., Carabasi, R.: Androgens and hepatocellular carcinoma, Lancet 1, 262, 1973;
Other side effects of the hormone-therapy:
Prelevic GM; Wurzburger MI; Balint-Peric L; Puzigaca Z , Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome, Gynecol Endocrinol (ENGLAND) Dec 1989 3 (4) p269-80; Navarro HA; Kudlacz EM; Eylers JP; Slotkin TA , Prenatal dexamethasone administration disrupts the pattern of cellular development in rat lung, Teratology (UNITED STATES) Nov 1989 40 (5) p433-8; Feldmann S; Minne HW; Parvizi S; Pfeifer M; Lempert UG; Bauss F; Ziegler R , Antiestrogen and antiandrogen administration reduce bone mass in the rat, Bone Miner (NETHERLANDS) Nov 1989 7 (3) p245-54; Townshend LM; Buckley EG , Linear subcutaneous fat atrophy after a single corticosteroid injection for ocular adnexal hemangioma, Am J Ophthalmol (UNITED STATES) Jan 15 1990 109 (1) p102-3; Simonin R; Nicolino-Peltier C; Gainlet P , Gonadorelin analogs combined with anti-androgens in the treatment of bone metastasis from prostate cancer. Can their use induce osteoporosis? (letter), Presse Med (FRANCE) Dec 9 1989 18 (41) p2023; Hou QC; Slotkin TA , Effects of prenatal dexamethasone or terbutaline exposure on development of neural and intrinsic control of heart rate, Pediatr Res (UNITED STATES) Dec 1989 26 (6) p554-7; Fernandez-Ruiz E; Rebollo A; Nieto MA; Sanz E; Somoza C; Ramirez F; Lopez- Rivas A; Silva A , IL-2 protects T cell hybrids from the cytolytic effect of glucocorticoids. Synergistic effect of IL-2 and dexamethasone in the induction of high-affinity IL-2 receptors, J Immunol (UNITED STATES) Dec 15 1989 143 (12) p4146-51; Tejkalova H; Benesova O; Kristofikova Z; Binkova B; Dlohozkova N; Buresova M , Behavioural teratogenic risk of perinatal administration of dexamethasone in combinations with phenoterol, Act Nerv Super (Praha) (CZECHOSLOVAKIA) Oct 1989 31 (3) p226-7 ; Meizner I; Katz M; Holcberg G; Insler V , Reduction or cessation of fetal movements after steroid administration for enhancement of lung maturation. II: Analysis of blood flow velocimetry, Isr J Med Sci (ISRAEL) Oct 1989 25 (10) p556-9; Mohan R; Muralidharan AR , Steroid induced glaucoma and cataract, Indian J Ophthalmol (INDIA) Jan-Mar 1989 37 (1) p13-6; Rivara G; Tomb RR; Foussereau J, Allergic contact dermatitis from topical corticosteroids, Contact Dermatitis (DENMARK) Aug 1989 21 (2) p83-91; Graf R; Gossrau R; Frank HG , Placental toxicity in rats after administration of synthetic glucocorticoids. A morphological, histochemical and immunohistochemical investigation, Anat Embryol (Berl) (GERMANY, WEST) 1989 180 (2) p121-30; Shimada H; Matsui M , Effects of intravitreal steroid injection on rabbit eye, Nippon Ganka Gakkai Zasshi (JAPAN) Apr 1989 93 (4) p501-10; Sylvester J; Fuentes RT; Holmes RA , Discordant radioaerosol/radioperfusion in drug-induced maternal pulmonary edema., Clin Nucl Med (UNITED STATES) Sep 1989 14 (9) p686-8; Mujeres y cardiopatia isquemica. Assmann G; Davignon J; Fernandez Cruz A; Gotto AM Jr; Jacotot B; Lewis B; Paoletti R, Women and ischemic cardiopathy, Rev Clin Esp (SPAIN) Oct 1989 185 (6) p308-15 ; Le Feuvre C; Baubion N; Berdah J; Heulin A; Vacheron A , Drug-induced cardiovascular complications, Ann Med Interne (Paris) (FRANCE) 1989 140 (7) p597-9; Nelson DA , Dangers from intraspinal steroid injections [letter], Arch Neurol (UNITED STATES) Mar 1990 47 (3) p255; Blaich G; Gottlicher M; Cikryt P; Metzler M , Effects of various inducers on diethylstilbestrol metabolism, drug-metabolizing enzyme activities and the aromatic hydrocarbon (Ah) receptor in male Syrian golden hamster liver, Steroid Biochem (ENGLAND) Feb 1990 35 (2) p201-4 ; Yamauchi T; Kokuho M; Yoshino S; Tachibana Y; Kawai T, Liver disorder owing to estrogen therapy in prostatic cancer. The correlation between serum level of cholinesterase and dose of diethylstilbestrol diphosphate, Nippon Hinyokika Gakkai Zasshi (JAPAN) Dec 1989 80 (12) p1713-9 ; Yamauchi T; Kokuho M; Yoshino S; Tachibana Y; Kawai T; Kitagawa T , Liver disorder owing to estrogen therapy in prostatic cancer, examined histopathologically in six autopsy cases, Nippon Hinyokika Gakkai Zasshi (JAPAN) Dec 1989 80 (12) p1706-12; Taweepoke P; Frame JD , Acute ischaemia of the hand following accidental radial artery infusion of Depo-Medrone, J Hand Surg [Br] (SCOTLAND) Feb 1990 15 (1) p118-20; Gardiner PV; Griffiths ID, Sudden death after treatment with pulsed methylprednisolone, BMJ (ENGLAND) Jan 13 1990 300 (6717) p125 ; Herishanu YO; Badarna S; Sarov B; Abarbanel JM; Segal S; Bearman JE , A possible harmful late effect of methylprednisolone therapy on a time cluster of optic neuritis, Acta Neurol Scand (DENMARK) Dec 1989 80 (6) p569-74; Juskowa J; Halweg H; Drac H; Smogorzewski M; Gorski A; Rancewicz Z; MaLdyk- Durlik M; Stryjecka-Rowinska D; PodsiadLo B; Kubicka-Pertkiewicz M, Cryptococcosis in patients with transplanted kidney treated with steroids and azathioprine, Pol Arch Med Wewn (POLAND) Aug-Sep 1988 80 (2-3) p113-23 ; Petcharuttana Y; Cutter GR; Meeks RG; Lorincz AE, Fluorescence microscopy of DES-induced morphologic transformation in unfixed, cultured cells, J Oral Pathol Med (DENMARK) Sep 1989 18 (8) p451-6; Ehrhardt AA; Meyer-Bahlburg HF; Rosen LR; Feldman JF; Veridiano NP; Elkin EJ; McEwen BS , The development of gender-related behavior in females following prenatal exposure to diethylstilbestrol (DES), Horm Behav (UNITED STATES) Dec 1989 23 (4) p526-41 ; Rivera Damm R; Ruiz MR; Perez Palacios G; Gaitan JR; Alonso MR, Physiopathology of amenorrhea caused by medroxyprogesterone acetate, Ginecol Obstet Mex (MEXICO) Dec 1977 42 (254) p359-67; Kanoh H; Hosono T; Matsui Y; Okudaira Y , Growth of endometrial cancer and hormone, Gan To Kagaku Ryoho (JAPAN) Dec 1989 16 (12) p3696-703; Walker BE, Tumors in female offspring of control and diethylstilbestrol-exposed mice fed high-fat diets, J Natl Cancer Inst (UNITED STATES) Jan 3 1990 82 (1) p50-4; Goldfarb S; Pugh TD, Morphology and anatomic localization of renal microneoplasms and proximal tubule dysplasias induced by four different estrogens in the hamster, Cancer Res (UNITED STATES) Jan 1 1990 50 (1) p113-9 ; Gray RH , Depot medroxyprogesterone and risk of breast cancer [letter], BMJ (ENGLAND) Oct 28 1989 299 (6707) p1099; Helmerhorst TJ; Wijnen HJ; Kenemans P; Tjioe GS; Dijkhuizen HH; Calame JJ; Stolk HG , Colposcopic findings and intraepithelial neoplasia in diethylstilbestrol- exposed offspring. The Dutch experience., Am J Obstet Gynecol (UNITED STATES) Nov 1989 161 (5) p1191-4 ; Shome GP; Sakauchi M; Yamane K; Takemura H; Kashiwagi H , Ischemic heart disease in systemic lupus erythematosus. A retrospective study of 65 patients treated with prednisolone, Jpn J Med (JAPAN) Sep-Oct 1989 28 (5) p599-603; Himeno Y; Fukuda Y; Hatanaka M; Imura H , Expression of oncogenes during rat chemical hepatotumorigenesis promoted by estrogen, J Cancer Res (NETHERLANDS) Aug 1989 80 (8) p737-42 ; van Gils AP; Tham RT; Falke TH; Peters AA , Abnormalities of the uterus and cervix after diethylstilbestrol exposure: correlation of findings on MR and hysterosalpingography, AJR Am J Roentgenol (UNITED STATES) Dec 1989 153 (6) p1235-8; Veldhuis JD , The estrogen-prolactinoma nexus in humans--fact or fable? [editorial] , Mayo Clin Proc (UNITED STATES) Sep 1989 64 (9) p1190-2; Scheithauer BW; Kovacs KT; Randall RV; Ryan N, Effects of estrogen on the human pituitary: a clinicopathologic study, Mayo Clin Proc (UNITED STATES) Sep 1989 64 (9) p1077-84 ; Inai K , An estrogen-dependent endogenous peroxidase in uterine epithelial cells of neonatal rats, Hiroshima J Med Sci (JAPAN) Dec 1981 30 (4) p311-38; Vessey MP, Epidemiological studies of the effects of diethylstilboestrol, IARC Sci Publ (FRANCE) 1989 (96) p335-48; Siminoski K; Goss P; Drucker DJ, The Cushing syndrome induced by medroxyprogesterone acetate, Ann Intern Med (UNITED STATES) Nov 1 1989 111 (9) p758-60; Nelson DA , Dangers from intraspinal steroid injections [letter], Arch Neurol (UNITED STATES) Mar 1990 47 (3) p255; Yamauchi T; Kokuho M; Yoshino S; Tachibana Y; Kawai T , Liver disorder owing to estrogen therapy in prostatic cancer. The correlation between serum level of cholinesterase and dose of diethylstilbestrol diphosphate, Nippon Hinyokika Gakkai Zasshi (JAPAN) Dec 1989 80 (12) p1713-9; Yamauchi T; Kokuho M; Yoshino S; Tachibana Y; Kawai T; Kitagawa T , Liver disorder owing to estrogen therapy in prostatic cancer, examined histopathologically in six autopsy cases, Nippon Hinyokika Gakkai Zasshi (JAPAN) Dec 1989 80 (12) p1706-12 ; Gardiner PV; Griffiths ID , Sudden death after treatment with pulsed methylprednisolone, BMJ (ENGLAND) Jan 13 1990 300 (6717) p125; Herishanu YO; Badarna S; Sarov B; Abarbanel JM; Segal S; Bearman JE , A possible harmful late effect of methylprednisolone therapy on a time cluster of optic neuritis, Acta Neurol Scand (DENMARK) Dec 1989 80 (6) p569-74; Juskowa J; Halweg H; Drac H; Smogorzewski M; Gorski A; Rancewicz Z; MaLdyk- Durlik M; Stryjecka-Rowinska D; PodsiadLo B; Kubicka-Pertkiewicz M , Cryptococcosis in patients with transplanted kidney treated with steroids and azathioprine, Pol Arch Med Wewn (POLAND) Aug-Sep 1988 80 (2-3) p113-23; Rivera Damm R; Ruiz MR; Perez Palacios G; Gaitan JR; Alonso MR, Physiopathology of amenorrhea caused by medroxyprogesterone acetate, Ginecol Obstet Mex (MEXICO) Dec 1977 42 (254) p359-67; Walker BE, Tumors in female offspring of control and diethylstilbestrol-exposed mice fed high-fat diets, J Natl Cancer Inst (UNITED STATES) Jan 3 1990 82 (1) p50-4; Goldfarb S; Pugh TD , Morphology and anatomic localization of renal microneoplasms and proximal tubule dysplasias induced by four different estrogens in the hamster, Cancer Res (UNITED STATES) Jan 1 1990 50 (1) p113-9; Gray RH, Depot medroxyprogesterone and risk of breast cancer [letter], BMJ (ENGLAND) Oct 28 1989 299 (6707) p1099; Helmerhorst TJ; Wijnen HJ; Kenemans P; Tjioe GS; Dijkhuizen HH; Calame JJ; Stolk HG , Colposcopic findings and intraepithelial neoplasia in diethylstilbestrol-exposed offspring. The Dutch experience, Am J Obstet Gynecol (UNITED STATES) Nov 1989 161 (5) p1191-4; Shome GP; Sakauchi M; Yamane K; Takemura H; Kashiwagi H , Ischemic heart disease in systemic lupus erythematosus. A retrospective study of 65 patients treated with prednisolone, Jpn J Med (JAPAN) Sep-Oct 1989 28 (5) p599-603; Himeno Y; Fukuda Y; Hatanaka M; Imura H , Expression of oncogenes during rat chemical hepatotumorigenesis promoted by estrogen, J Cancer Res (NETHERLANDS) Aug 1989 80 (8) p737-42; ; Siminoski K; Goss P; Drucker DJ , The Cushing syndrome induced by medroxyprogesterone acetate, Ann Intern Med (UNITED STATES) Nov 1 1989 111 (9) p758-60; Fornander T; Rutqvist LE, Adjuvant tamoxifen and second cancers [letter], Lancet (ENGLAND) Mar 18 1989 1 (8638) p616; Nemerov EV , A case of corticosteroid-induced myocarditis in a patient with bronchial asthma, Klin Med (Mosk) (USSR) Dec 1988 66 (12) p96-7; Saksonov SI; Meshcheriakova EV; Baras ES; Beker OM, Corticosteroid tuberculosis, Klin Med (Mosk) (USSR) Dec 1988 66 (12) p93-6; Rytter M; Walther T; Suss E; Haustein UF, Allergic reactions of the immediate and delayed type following prednisolone medication, Dermatol Monatsschr (GERMANY, EAST) 1989 175 (1) p44-8; Vick NA , Steroid toxicity [letter] , J Neurooncol (UNITED STATES) Sep 1988 6 (2) p199; Ruch W; Jenny P , Priapism following testosterone administration for delayed male puberty [letter], Am J Med (UNITED STATES) Feb 1989 86 (2) p256; Love RR , The Wisconsin Tamoxifen Study: toxicity in node-negative postmenopausal women, Cancer Invest 1988 6 (5) p601-5; Wanachiwanawin W; Visudhiphan S; Piankijagum A; Vatanavicharn S , Serious complications following treatment of chronic idiopathic thrombocytopenic purpura, Postgrad Med J (ENGLAND) Jun 1988 64 (752) p426-30; Fornander T; Rutqvist LE; Cedermark B; Glas U; Mattsson A; Silfversward C; Skoog L; Somell A; Theve T; Wilking N; et al , Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers., Lancet Jan 21 1989 1 (8630) p117-20; Bruning PF; Bonfrer JM; Hart AA; de Jong-Bakker M; Linders D; van Loon J; Nooyen WJ, Tamoxifen, serum lipoproteins and cardiovascular risk, Br J Cancer (ENGLAND) Oct 1988 58 (4) p497-9 ; Hardell L , Pelvic irradiation and tamoxifen as risk factors for carcinoma of corpus uteri [letter], Lancet Dec 17 1988 2 (8625) p1432; Bischoff C, Epidural lipomatosis as a complication of a long-term glucocorticoid therapy, Dtsch Med Wochenschr (GERMANY, WEST) Dec 16 1988 113 (50) p1964-7; Puntis JW; Morgan ME; Durbin GM , Dexamethasone-induced bradycardia [letter] , Lancet (ENGLAND) Dec 10 1988 2 (8624) p1372; deVoogt HJ; Pavone-Macaluso M; Sylvester R; Schroder FH , Re: Cardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer Trials 30761 and 30762 [letter], J Urol Dec 1988 140 (6) p1557; Jerome CP; Hendrickx AG, Comparative teratogenicity of triamcinolone acetonide and dexamethasone in the rhesus monkey (Macaca mulatta), J Med Primatol 1988 17 (4) p195-203 ; Dhingra K; Newcom SR , Acute tumor lysis syndrome in non-Hodgkin lymphoma induced by dexamethasone, Am J Hematol Oct 1988 29 (2) p115-6; Ohlsson A; Heyman E , Dexamethasone-induced bradycardia [letter], Lancet (ENGLAND) Nov 5 1988 2 (8619) p1074; Sechi GP; Piras MR; Demurtas A; Tanca S; Rosati G, Dexamethasone-induced schizoaffective-like state in multiple sclerosis: prophylaxis and treatment with carbamazepine., Clin Neuropharmacol (UNITED STATES) Oct 1987 10 (5) p453-7 ; Yasumura T; Oka T; Honjo H; Okada H, Menstrual abnormality in patients with breast cancer receiving adjuvant endocrine-chemotherapy, Gan To Kagaku Ryoho Oct 1988 15 (10) p2947-52; Haar D, Binswanger's disease after prednisolone and azathioprine therapy, Acta Neurol Scand Jul 1988 78 (1) p76-7; Horn PL; Thompson WD, Exposure to chemotherapeutic agents and the risk of a second breast cancer: preliminary findings, Yale J Biol Med May-Jun 1988 61 (3) p223-31; Mayer G; Watschinger B; Pohanka E; Graf H; Popow T; Ulrich W; Kovarik J, Cytomegalovirus infection after kidney transplantation using cyclosporin A and low-dose prednisolone immunosuppression, Nephrol Dial Transplant (GERMANY, WEST) 1988 3 (4) p464-8; Vogelgesang SA; McMillin JM, Hypocalcemia associated with estrogen therapy for metastatic adenocarcinoma of the prostate, J Urol Nov 1988 140 (5) p1025-7 ; Kyle V; Hazleman BL , Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects, Ann Rheum Dis Aug 1989 48 (8) p662-6 ; John GT; Thomas PP; Kirubakaran MG; Thomas M; Jacob CK; Shastry JC , Methylprednisolone sodium succinate-induced anaphylaxis in a nonatopic renal transplant recipient [letter], Transplantation (UNITED STATES) Sep 1989 48 (3) p543; Neumann F; Bormacher K; Radlmaier A , Differences in action and toxicity of antiandrogens, Prog Clin Biol Res (UNITED STATES) 1989 303 p123-8; d'Orban PT , Steroid-induced psychosis, Lancet (ENGLAND) Sep 16 1989 2 (8664) p694 ; Clarke R; van der Berg HW , Adverse interactions between cytotoxic drugs and hormonal agents in human breast cancer cells [letter], J Clin Oncol (UNITED STATES) Oct 1989 7 (10) p1580-2 ; Levine M , Thromboembolic risk of tamoxifen in patients with stage II breast cancer [letter], J Clin Oncol Oct 1989 7 (10) p1579-80; Gladek A; Liehr JG , Mechanism of genotoxicity of diethylstilbestrol in vivo, J Biol Chem (UNITED STATES) Oct 5 1989 264 (28) p16847-52; Edelman DA , Diethylstilbestrol exposure and the risk of clear cell cervical and vaginal adenocarcinoma., Int J Fertil Jul-Aug 1989 34 (4) p251-5 ; Combes B , Prednisolone for primary biliary cirrhosis--good news, bad news, Hepatology (UNITED STATES) Oct 1989 10 (4) p511-3; Mitchison HC; Bassendine MF; Malcolm AJ; Watson AJ; Record CO; James OF , A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss, Hepatology Oct 1989 10 (4) p420-9; Fan CJ; Goh KL; Wang F , Steroid induced exophthalmos. A case report, Australas Radiol May 1989 33 (2) p182-3; Sambrook PN; Cohen ML; Eisman JA; Pocock NA; Champion GD; Yeates MG , Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study, Ann Rheum Dis Jul 1989 48 (7) p535-8; Key LL; Myers MC; Kroovand RL; Kelly WS , Priapism following testosterone therapy for delayed puberty [letter], Am J Dis Child (UNITED STATES) Sep 1989 143 (9) p1001-2 ;
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Foot-notes
(1) PARK, W.W., LEES, J.C., The absolute curability of Cancer of the breast, Surg. Gynec. Obstet., 1951, 93: 152;
DURRANT, K.R., ELLIS, F., BLACK, J.M., BERRY, R.J., RIDEHALGH, F.R., HAMILTON, W.S., Comparison of treatment policies in inoperable bronchial carcinoma, Lancet, 1971, 1: 715-719;
ZUMOFF, B., HELLMAN, L., The possibility of predicting the efficacy of cancer chemotherapy in the prolongation of survival, Lancet, 1967, 1: 878-880;(2) SUTHERLAND, R., Cancer. The significance of delay, Butterworths, London, 1960;
TAUSCOTT, B.M., Br. J. Cancer, 1947, 1: 129;
BLOOM, H.J.G., Br. J. Cancer, 1950, 4: 347;
MACDONALD, I.G., Surg. Gynec. Obstet., 1951, 92: 443;
Mc KINNON, N.E., Control of Cancer mortality, Lancet, 1954, 1: 251;
FRANKS, L.M., Latency and Progression in Tumors. The Natural of Prostatic Cancer, Lancet, 1956, 2: 1039;
BLOOM, H.J.G., Natural History of untreated breast cancer, Ann. N.Y. Acad. Sci., 1964, 114: 747;
EISENBERG, H., Trends in survival of digestive system cancer patients in Connecticut, 1935-1962, Gastroenterol., 1967, 53: 528;
STEVENS, A.R., Jr., Lymphatic leukemia for perhaps 28 years, N. Engl. J. Ned., 1969, 281: 448.(3) Statistical data are taken from : BUENTE, H., Krebs ist heilbar... wenn Sie selbst die Früherkennung ermöglichen, Perimed Verlag, Erlangen, 1976.:
(4) World Health Organization, Weekly Epidemio-logical Record, April 26th, 1985, 60th year, 125-129.
(5) Australia, Austria, Belgium, Bulgaria, Canada, Czechoslovakia, Denemark, Finland, France, Germany (Federal Republic of), Greece, Hungary, Iceland, Ireland, Italy, Japan, the Netherlands, New Zealand, Norway, Poland, Portugal, Roumania, Spain, Sweden, Zwitzerland, Yugoslavia, the United Kingdom and the United States of America.
(6) See also LOGAN, W.P.D., Le Cancer du sein toujours aussi meurtrier, Chronique O.M.S. (W.H.O.), 1975, 29: 505-514.
(7) Weekl. Epidem. Rec., ibid.
(8) FINNEY, G.G., MERKEL, W.C., MILLER, D.B., Carcinoma of the breast: a study of 298 consecutive cases, Ann. Surg., 1947, 125: 673-687;
KOTHARI, M.L., NEHTA, L.A., Kanker. Fabels en Feiten, Het Wereldvenster, Bussum, p.50;(9) PARK, W.W., LEES, J.C., The absolute curability of cancer of the breast, Surg. Gynec. Obstet., 1951, 93: 129;
Osteosarcoma: advance in treatment or changing natural history ?, Lancet, 1978, 2: 82-83;(10) CULLITON, B.J., Mammography controversy: N.I.H.'s entré into evaluating technology, Science, 1977, 198: 172;
BUNKER, J.P., DONAHUE, V.C., COLE, Ph., NOTMAN, M.T., Elective hysterectomy: pro and con, N. Engl. J. Med., 1976, 295: 264-8;(11) Mc KINNON, N.E., o.p., p. 254
(13) GOLDENBERG, G.J., et al., Cancer Res., 1971; 31: 1616; Cancer Res., 1974; 34: 3274.
(14) The information that concern the side effects of remedies are retained from authoritative documents like A.M.A. Drug Evaluation, 1977; American Hospital Formulary Service, 1978; Martindale's The Extra Pharmacopeia, 1977; Meyeler's Side Effects of Drugs, VIII; Physician's Desk Reference, 1979; Remington's Pharma-ceutical Sciences, 1975. A reference was made only when specific liturature was found.
(15) KROESE, W.F. Stenfert. Cytostatic Drugs, Meyler's Side Effects of Drugs, VI. M.N. Duke, ed. New York, American Elsevier Publishing Co., Inc., 1976: 447.
Dr. Henri ROSENBERG, LL.D., Ph.D., N.D.
Doctor of Naturopathy
Permanent Member of the British
Guild of Drugless Practitioners.
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