Long-term cyclophosphamide treatments against primary mammary tumors in C3H/He mice.

Tumor-free inbred female C3H/He mice were given weekly injections of cyclophosphamide to prevent or delay the expected occurrence of spontaneous mammary carcinomas. Chemotherapy was started at an age when the mice would already have developed preneoplastic hyperplastic alveolar nodules and tumors were likely to appear within a few weeks. Treatments were given for periods ranging from 10 to 50 weeks with various schedules and doses. The mice were observed for the development of tumors until they died or were killed. Tumors were excised as they appeared. Treatments were most effective in reduction of the number of primary tumors when started early and given continuously. Longer term, low-dose treatments gave better results than short-term, high-dose treatments, although the total dose given was the same. The prophylactic effect of the drug appeared to be by the destruction of occult, drug-sensitive tumors, rather than by delay of their appearance. The toxicity of moderate, continuous drug administration was well tolerated with no mortality and only minor transient weight loss.