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. 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