A five-alpha reductase inhibitor or an antiandrogen prevents the progression of microscopic prostate carcinoma to macroscopic carcinoma in rats

Abstract

of 5-alpha reductase inhibitor (e.g., finasteride) and a pure antiandrogen (e.g., Hideyuki Akaza 1 casodex) on rat prostate carcinogenesis and to determine whether latent prostate Mizuki Onozawa 1 carcinoma can be prevented to develop to clinically significant cancer by use of Tomoyuki Shirai 2 these drugs. Yukitaka Ideyama 3 METHODS. F344 rats were subcutaneously administered 3,2-dimethyl-4-aminobi-phenyl (DMAB) for the first 20 weeks and testosterone propionate throughout the 1 Department of Urology, Institute of Clinical 60-week study. Finasteride (5 mg/kg and 15 mg/kg, 2 times per week) and casodex Medicine, University of Tsukuba, Tsukuba, Ibar-(15 mg/kg, 30 mg/kg, and 60 mg/kg, 3 times per week) were administered orally aki, Japan. during the last 40 weeks of the study. Tumors were classified as visible prostate 2 First Department of Pathology, Nagoya City carcinoma when they could be recognized with the naked eye and as microscopic University, Nagoya, Aichi, Japan. prostate carcinoma when detectable only with a microscope. 3 Endocrinology and Metabolic Disease Re-RESULTS. The incidence of visible prostate carcinoma was 51% (18 of 35 rats) in search Laboratory, Institute for Drug Discovery the positive control group, whereas it was 40% (4 of 10 rats) in the finasteride 5 Research, Yamanouchi Pharmaceutical Co., mg/kg group, 16.7% (2 of 12 rats, P Å 0.0091) in the finasteride 15 mg/kg group, Ltd., Tsukuba, Ibaraki, Japan. 20% (4 of 20 rats, P Å 0.05) in the casodex 15 mg/kg group, 14.3% (3 of 21 rats, P Å 0.0008) in the casodex 30 mg/kg group, and 0% (0 of 11 rats, P Å 0.0002) in the casodex 60 mg/kg group. On the other hand, when visible carcinomas and microscopic carcinomas were handled together, only casodex 60 mg/kg significantly inhibited the carcinogenesis rate. CONCLUSIONS. Finasteride achieved dose-dependent inhibition of macroscopic rat prostate carcinogenesis, and casodex also inhibited macroscopic prostate carcino-genesis. However, both drugs showed insufficient prevention of carcinogenesis at the microscopic level. These findings indicate that, in clinical medicine as well, such drugs may also be able to prevent the progression of latent prostate carcinoma to life-threatening disease.

Suppressive effects of antiandrogens, finasteride and flutamide on development of prostatic lesions in a transgenic rat model

“…TRAP lesions have many advantages, for example, their large size allows adequate materials to be obtained and development of prostate cancer occurs in a shorter experimental period and more efficiently compared with several other rat prostate carcinogenesis models. [11][12][13][14][15][16][17][18][19] These characteristics of TRAP may make it particularly suitable for evaluation of strategies for chemoprevention and treatment. The present study was conducted to assess whether finasteride and flutamide have the ability to suppress prostate carcinogenesis in our TRAP model.…”

Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy.

“…Another explanation might be understaging of prostate cancer at initial diagnosis. 6 Another interesting aspect in our patient's case was her moderate response to anti-androgens (flutamide), which may suggest the existence of an active androgen receptor (AR) pathway. Few studies have shown that AR is commonly expressed in prostate cancer with increased levels after androgen deprivation.…”

Genetic Epidemiology of Hereditary Prostate Cancer in Finland

“…There are some experimental data suggesting that chemoprevention may decrease the risk of prostate cancer (Tsukamoto et al, 1998). Also studies on the use of 5-alpha reductase treatment in chemoprevention of prostate cancer are ongoing (Brawley and Parnes, 2000).…”