Preclinical evaluation of toxicity and therapeutic efficacy of a stabilized cytostatic metabolite of cyclophosphamide (ASTA Z 7557, INN mafosfamide).

Abstract

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.

• Authors: H O Klein, P D Wickramanayake, E Christian, C Coerper
• Journal: Investigational new drugs (Invest New Drugs) Vol. 2 Issue 2 Pg. 191-9 ( 1984) ISSN: 0167-6997 [Print] United States
• PMID: 6469514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Asta Z 7557
• Cyclophosphamide

Topics

• Animals
• Carcinoma, Ehrlich Tumor (drug therapy)
• Cell Division (drug effects)
• Cyclophosphamide (analogs & derivatives, pharmacology, therapeutic use, toxicity)
• Drug Evaluation, Preclinical
• Humans
• Lethal Dose 50
• Lung Neoplasms (drug therapy)
• Male
• Mammary Neoplasms, Experimental (drug therapy)
• Melanoma (drug therapy)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy, mortality)
• Stomach Neoplasms (drug therapy)
• Transplantation, Heterologous