BIOLOGICAL ASPECTS OF ANTIANDROGENS

Abstract

Flutamide (α,α,α-trifluoro-2–methyl-4′-nitro-m-propionotoluidide) at daily doses from 1-50 mg/kg reduced seminal vesicle and ventral prostate weights of intact male rats. A comparative study in castrated rats revealed that flutamide was equipotent to cyproterone acetate (CPA) as an antiandrogen. These potencies were substantiated by a newly developed assay measuring DNA synthesis rate (Sufrin and Coffey). No androgenic, estrogenic, anti-estrogenic, corticoid, progestational, anti-progestational, or antigonadotrophic activities were observed. Flutamide, given per os daily for either 6 weeks or 1 year to aged dogs with benign prostatic hyperplasia, reduced prostatic size in 6 weeks and the prostate remained reduced at 3, 6 and 12 months after the initiation of drug therapy. Flutamide, given im three times weekly for 4 weeks reduced the size of the baboon prostate (Müntzing et al.). In testosterone propionate-treated castrated rats CPA and flutamide inhibited 3H-testosterone uptake and retention by prostate and prostate nuclei. In a study in 18 patients with far-advanced carcinoma of the prostate, there were seven positive responders, 10 failures and one inconclusive report, following the daily administration of flutamide (Stoliar and Albert). In a similar study, 9 of 12 patients in stage D prostatic carcinoma responded favorably (Prout and Irwin).