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.