Antitumor effect and metabolic activation of cyclophosphamide and 4-hydroperoxycyclophosphamide in the human breast carcinoma (MX-1)-nude mouse system.

The effects of cyclophosphamide (CPA) and its active form, 4-hydroperoxy-CPA, against human breast carcinoma transplanted into nude mice (BALB/c nu/nu) were evaluated in terms of the decreases of hepatic drug-metabolizing enzymes in nude mice. A human breast carcinoma, MX-1, was implanted into the subcutaneous tissue of nude mice and a drug was administered intravenously once at a dose of 0.05, 0.1 or 0.15 mmol/kg, 1 or 3 weeks after tumor inoculation. 4-Hydroperoxy-CPA was more effective than CPA as regards inhibition of tumor growth, and the difference in effect was greater when the drugs were administered 3 weeks after tumor inoculation. The activity of CPA was depressed by the decrease of the hepatic drug-metabolizing enzymes in proportion to the tumor-bearing period. Therefore, the effects of masked derivatives of CPA may correlate with the changes in drug-metabolizing activities of tumor-bearing mice. The human tumor xenografts-nude mice system is considered to be suitable for chemosensitivity tests with masked compounds.