A 5-ALPHA REDUCTASE INHIBITOR OR AN ANTIANDROGEN PREVENTS THE PROGRESSION OF MICROSCOPIC PROSTATE CARCINOMA TO MACROSCOPIC CARCINOMA IN RATS

BACKGROUND. The objective of this study was to elucidate the prophylac tic effects of 5-alpha reductase inhibitor (e.g., finasteride) and a p ure antiandrogen (e.g., casodex) on rat prostate carcinogenesis and to determine whether latent prostate carcinoma can be prevented to devel op to clinically significant cancer by use of these drugs. METHODS. F3 44 rats were subcutaneously administered 3,2'-dimethyl-4-aminobiphenyl (DMAB) for the first 20 weeks and testosterone propionate throughout the 60-week study. Finasteride (5 mg/kg and 15 mg/kg, 2 times per week ) and casodex (15 mg/kg, 30 mg/kg, and 60 mg/kg, 3 times per week) wer e administered orally during the last 40 weeks of the study. Tumors we re classified as visible prostate carcinoma when they could be recogni zed with the naked eye and as microscopic prostate carcinoma when dete ctable only with as microscope. RESULTS. The incidence of visible pros tate carcinoma was 51% (18 of 35 rats) in the positive control group, whereas it was 40% (4 of 10 rats) in the finasteride 5 mg/kg group, 16 .7% (2 of 12 rats, P = 0.0091) in the finasteride 15 mg/kg group, 20% (4 of 20 rats, P = 0.05) in the casodex 15 mg/kg group, 14.3% (3 of 21 rats, P = 0.0008) in the casodex 30 mg/kg group, and 0% (0 of 11 rats , P = 0.0002) in the casodex 60 mg/kg group. On the other hand, when v isible carcinomas and microscopic carcinomas were handled together, on ly casodex 60 mg/kg significantly inhibited the carcinogenesis rate. C ONCLUSIONS. Finasteride achieved dose-dependent inhibition of macrosco pic rat prostate carcinogenesis, and casodex also inhibited macroscopi c prostate carcinogenesis. However, both drugs showed insufficient pre vention of carcinogenesis at the microscopic level. These findings ind icate that, in clinical medicine as well such drugs may also be able t o prevent the progression of latent prostate carcinoma to life-threate ning disease. (C) 1998 American Cancer Society.