[Selective toxicity of cytostatic agents: studies on the cardiotoxicity of doxorubicin, its pathogenesis and contraindications].
In the past few years the medical treatment of malignant diseases has steadily increased in scope and importance. However, the tumor regimens described in the textbooks still are rather schematic recommendations, which are inadequately tailored to the needs of the individual case. Current tumor therapy is based on the results of the statistical analysis using empirical data collected in randomized trials. While patients can today be given a statistical value which expresses their computed chance of a cure versus that of a defined population, there is still no generally valid method which could serve as a rational basis for individualized counselling. But cytostatic chemotherapy has yet another major shortcoming: the collective assessment of toxicity, which is related to one of the basic properties of cytostatic drugs, i.e. their extremely low therapeutic index. Many of the side effects of cytostatics may cause severe irreversible, at times even fatal, organ dysfunction. Consequently, the definition of the therapeutic risks involved on the basis of an objective identification of potential organ toxicity is a major challenge. "Surgery without a knife", as K.H. Spitzy has called chemotherapy, should be subjected to objective criteria for its indications and contraindications so that patients can truly benefit from what are become increasingly aggressive measures. The principle of weighing the benefits desired in the individual case against the potential risks involved in a specific treatment, which Paul Ehrlich postulated for antibacterial chemotherapy, should also be applied to cytostatic chemotherapy with a view to facilitating the decision for or against therapy in borderline cases. The present contribution which is designed to shed light on the cardiotoxicity of doxorubicin should be interpreted in light of this situation. Pathogenetic aspects and animal experiments on drug-induced lipid peroxidation will be discussed and clinical trials on both acute and chronic doxorubicin cardiotoxicity will be reviewed. Special attention will be paid to the tolerable risks of this special form of toxicity and cardiologic methods currently available for patient monitoring will be critically assessed. In summary, the studies produced the following results: A. Pathogenesis Treatment of C 57 B1 mice with doxorubicin increases the production of malonic dialdehyde in the myocardium. Enhanced malonic dialdehyde production can largely be suppressed by the additional administration of anti-oxidants (tocopherol, glutathione, cysteamine, cysteine).(ABSTRACT TRUNCATED AT 400 WORDS)
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000792:Angiography; D000818:Animals; D001669:Biochemical Phenomena; D001671:Biochemistry; D001943:Breast Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy; D006328:Cardiac Catheterization; D005117:Cardiac Complexes, Premature / Q000139:chemically induced; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity*; D004791:Enzyme Inhibitors; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000032:analysis; D011877:Radionuclide Imaging; D012306:Risk
D004791:Enzyme Inhibitors; D008315:Malondialdehyde; D004317:Doxorubicin; D000251:Adenosine Triphosphatases
Zur selektiven Toxizität von Zytostatika: Untersuchungen zur Doxorubicinkardiotoxizität, ihre Pathogenese und Kontraindikationsstellung.