Combined finasteride and flutamide therapy in men with advanced prostate cancer

Objectives. To evaluate the efficacy of combined finasteride and flutamide therapy in men with advanced prostate cancer by determining (1) the short-term tolerability of finasteride monotherapy and its effect on serum prostate-specific antigen (PSA) and hormone (testosterone, dihydrotestosterone) levels, and (2) the effects of the addition of flutamide on tolerability and on serum PSA and hormone levels. Methods. Thirteen 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 radical 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. Results. Finasteride alone (median 5 weeks) had no significant effect on serum PSA levels (P >0.05). Combined finasteride and flutamide resulted in 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 undetectable levels (0.2 ng/mL or less). Finasteride alone had no significant effect on serum testosterone levels (P >0.05) but did result in a mean 74% reduction in serum dihydrotestosterone levels. Combined finasteride and flutamide resulted in a mean 56% increase in serum testosterone levels but had no additional effect on serum dihydrotestosterone levels (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 Combined finasteride and flutamide therapy was withdrawn from 15% (2 of 13) because of flutamide-induced diarrhea and from 23% (3 of 13) because of disease progression. 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 received combined finasteride and flutamide for a median 11 months (range 6 to 19). Conclusions. Finasteride monotherapy is inadequate therapy for advanced prostate cancer, but combined finasteride and flutamide may be a reasonable alternative for men with advanced prostate cancer who refuse conventional hormone therapy. Copyright 1996 by Elsevier Science Inc.