The Ambivalence of Cytostatic Therapy

E. GRUNDMANN The question as to whether cytostatic drugs might be carcinogenic has been presented and discussed in three experimental studies. The most extensive in vestigations were by J. H. WEISBURGER and coll. (New York, Alabama, Bethesda). They started with an exact determination of rate and localization for spon- . taneous tumors in their animal strains. Thirteen cytostatic compounds current ly in clinical use were then given in the maximally tolerated dose (MTD) to groups of 25 male and 25 female animals (rats and mice) three times weekly, in most assays over a period of 6 months. Other identical groups of animals received 0. 5 of the MTD. Each test involved 50 male and 50 female mice and the same number of rats. As positive controls, identical groups were given diethylnitrosamine, which induced tumors of liver, lungs and kidneys in the expected rates. The direct alkylating agents (Actinomycin 0, Melphalan, Mito mycin 0, Uracil mustard, Dibromomannitol and Dibromodulcitol) induced cancer in the peritoneal cavity, the site of the injections. Rats appeared to be more susceptible than mice. Other drugs (e. g. the cyclohexamide salt of phos phorodiamidic acid derivative, Natulan, DIC and streptozotocin) had a broad spectrum of carcinogenicity affecting a variety of organs. Several agents led to tumors in the hematopoietic and lymphatic systems in mice or rats or both. The correlation to the general immunosuppressive action is not quite clear. 6-Mercaptopurine induces lymphosarcomas in mice.

Klappentext

Gesellschaft zur Bekämpfung der Krebskrankheiten, Nordrhein- Westfalen e.V. and European Organization for Research on Treatment of Cancer. 5. Symposium in Düsseldorf, November 8, 9, 1973

Inhalt
I. Tumor Induction by Cytostatics?.- The Carcinogenic Properties of Some of the Principal Drugs Used in Clinical Cancer Chemotherapy.- Experimental Investigations with Anti-Cancer Drugs for Carcinogenicity with Special Reference to Immunedepression.- Tests for Tumor Induction by Antitumor Agents.- Adverse Reactions to Cytostatic Agents.- The Changing Pattern of Hodgkin's Disease Seen at Autopsy.- Tumor Inductions by Cytostatics in Man.- Methodological Problems in the Quantitative Assessment of Carcinogenesis in Long-Term Studies.- Summary.- II Tumor Induction by Immunodeficiency?.- Immune Suppression and Chemical Carcinogenesis.- Experimental Investigations on Immunodepressive Properties of Carcinogenic Substances in Male Sprague-Dawley Rats.- The Significance of Immunosuppression and Antigenic Stimulation in the Development of Malignant Lymphomas.- Malignant Disease in Immunodeficient States in Man.- The Effect of Cytostatic Therapy on Cellular Immunity in vitro.- The Balance of Host Immunocompetence in Chemical Carcinogenesis and Nonspecific Immunotherapy.- Tumor Induction in Immunologically Privileged Sites.- Patterns of Neoplastic and Nonneoplastic Diseases of Praomys (Mastomys) Natalensis.- Summary.- III. Cell Synchronization in Tumor Therapy.- The Cell Cycle in Cancer Chemotherapy.- Proliferative Parameters Relevant to Cancer Therapy.- Different Types of DNA-Synthesis and Their Importance in Cancer Growth and Therapy.- Investigations on Partial Synchronization in Ascites Tumors of Different Ploidy and in Solid Transplantable Tumors.- Critical Survey of Experimental Data on in vivo Synchronization by Hydroxyurea.- Cell Synchronization in Solid Tumors.- Experimental and Clinical Results of Chemotherapy after Partial Synchronization of Cell Proliferation.-Problems in the Treatment of Slow-Growing Tumors.- Summary.