COMBINED FINASTERIDE AND FLUTAMIDE THERAPY IN MEN WITH ADVANCED PROSTATE-CANCER

Objectives. To evaluate the efficacy of combined finasteride and fluta mide therapy in men with advanced prostate cancer by determining (1) t he short-term tolerability of finasteride monotherapy and its effect o n serum prostate-specific antigen (PSA) and hormone (testosterone, dih ydrotestosterone) levels, and (2) the effects of the addition of fluta mide on tolerability and on serum PSA and hormone levels. Methods. Thi rteen hormone-naive men with advanced prostate cancer (4 with Stage D2 , 1 with Stage D1, with Stage DO, and 7 with rising PSA levels after r adical prostatectomy [n = 2] or definitive radiation therapy [n = 5]) were initially treated with 5 mg finasteride daily. Flutamide (250 mg three times a day) was added after serum PSA levels stabilized. Result s. Finasteride alone (median 5 weeks) had no significant effect on ser um PSA levels (P >0.05). Combined finasteride and flutamide resulted i n a mean 91% reduction in serum PSA levels, with 85% of men achieving a nadir serum PSA level of less than 4.0 ng/mL and 46% achieving undet ectable levels (0.2 ng/mL or less). Finasteride alone had no significa nt effect on serum testosterone levels (P >0.05) but did result in a m ean 74% reduction in serum dihydrotestosterone levels. Combined finast eride and flutamide resulted in a mean 56% increase in serum testoster one levels but had no additional effect on serum dihydrotestosterone l evels (P > 0.05). Side effects occurred in 85% (gynecomastia or breast tenderness in 62% [8 of 13] and diarrhea in 25% [3 of 13]) of men on combined therapy. Potency was preserved in 66%. Combined finasteride a nd flutamide therapy was withdrawn from 15% (2 of 13) because of fluta mide-induced diarrhea and from 23% (3 of 13) because of disease progre ssion. All remaining patients (8 of 13) have serum PSA levels below 4. 0 ng/mL and 4 of these 8 have undetectable levels. These men have rece ived combined finasteride and flutamide for a median 11 months (range 6 to 19). Conclusions. Finasteride monotherapy is inadequate therapy f or advanced prostate cancer, but combined finasteride and flutamide ma y be a reasonable alternative for men with advanced prostate cancer wh o refuse conventional hormone therapy. Copyright 1996 by Elsevier Scie nce Inc.