Therapy of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas with combinations of 5-fluorouracil and 2 alpha-methyldihydrotestosterone propionate.
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.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000732:Androstanols / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice
D000732:Androstanols; D015127:9,10-Dimethyl-1,2-benzanthracene; C100263:dromostanolone; D005472:Fluorouracil; C007561:dromostanolone propionate