Therapy of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas with combinations of 5-fluorouracil and 2 alpha-methyldihydrotestosterone propionate

• Published in: Cancer research (Chicago, Ill.) Ill.), 1982-11, Vol.42 (11), p.4408
• Main Authors: Teller, M N, Stock, C C, Bowie, M, Chou, T C, Budinger, J M
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Androstanols - analogs & derivatives; Androstanols - therapeutic use; Animals; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Fluorouracil - therapeutic use; Mammary Neoplasms, Experimental - chemically induced; Mammary Neoplasms, Experimental - drug therapy; Mice
• ISSN: 0008-5472

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 alpha-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/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.