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Therapy of 7,12-Dimethylbenz(a)anthracene-induced Rat Mammary Carcinomas with Combinations of 5-Fluorouracil and 2-Methyldihydrotestosterone Propionate¹

Sloan-Kettering Institute for Cancer Research, New York 10021 [M. N. T., C. C. S., M. B., T-C. C.], and Lawrence Hospital, Bronxville 10708 [J. M. B.], New York

This investigation was undertaken to determine whether a combination of a cytotoxic drug with a sex hormone would provide efficacious therapy for mammary carcinomas. Established, 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas were treated with 5-fluorouracil (5-FUra) and 2-methyldihydrotestosterone propionate (MDTP) for 4 weeks. At end of therapy, pooled data showed 21% of the tumors in complete remission (CR) in rats given 5-FUra at 17.5 mg/kg/day and 3% in those given 8 mg/kg/day. Administration of MDTP at 1.25 to 5 mg/kg/day yielded 15 to 48% tumor CR. The combination of 5-FUra at 17.5 mg/kg/day with MDTP at 5, 2.5, and 1.25 mg/kg/day induced, respectively, 96, 91, and 75% CR. Maxima of 100, 100, and 92% CR were obtained in single tests at these respective doses. Therapy with combinations of 5-FUra at 8 mg/kg/day and MDTP at 2.5 and 1.25 mg/kg/day yielded, respectively, 69 and 61% tumor CR. Appearance of new tumors during and after therapy was controlled more effectively by combinations of the two agents. Analysis of percentage of tumor CR showed marked synergism for 5-FUra and MDTP. A second course of combination therapy effectively prolonged duration of CR. Therapy with the cytotoxic drug 5-FUra in combination with the androgen analog MDTP is highly efficacious against induced mammary carcinomas.

¹ Supported in part by Grants CA 18856 and CA 27569 and by Core Grant 08748 awarded by the National Cancer Institute. Presented in part at the Annual Meeting of the American Association for Cancer Research, San Diego, Calif., May 1980 (29).

² To whom requests for reprints should be addressed, at Donald S. Walker Laboratory, Sloan-Kettering Institute for Cancer Research, Rye, N. Y. 10580.

Received 11/23/81. Accepted 8/ 2/82.