Preclinical evaluation of toxicity and therapeutic efficacy of a stabilized cytostatic metabolite of cyclophosphamide (ASTA Z 7557, INN mafosfamide).
ASTA Z 7557 is a stabilized cytostatic metabolite of cyclophosphamide which forms crystals at room temperature and releases 4-OH-cyclophosphamide in aqueous solution. The LD50/30 in mice after push injection is 417 mg/kg, after fractionated administration (q 6 hours X 4) 794 mg/kg. Daily treatment times 5 gives a LD50/30 value of 200 mg/kg. Depression of nucleated bone marrow cells and of leukocytes in the peripheral blood is observed after treatment. Recovery is slow. This holds true for push and fractionated administration. ASTA Z 7557 is a powerful cytostatic drug for treatment of an Ehrlich ascites tumor, a Lewis lung and a mammary carcinoma. Of two human tumor xenografts a malignant amelanotic melanoma responded with slight growth delay, whereas a gastric cancer did not.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007928:Lethal Dose 50; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D013274:Stomach Neoplasms / Q000188:drug therapy; D014183:Transplantation, Heterologous
C037933:Asta Z 7557; D003520:Cyclophosphamide