FINASTERIDE AND FLUTAMIDE AS POTENCY-SPARING ANDROGEN-ABLATIVE THERAPY FOR ADVANCED ADENOCARCINOMA OF THE PROSTATE

Objectives. Androgen ablation with luteinizing hormone-releasing hormo ne (LHRH) agonists, orchiectomy, or oral estrogens has significant unt oward sexual side effects. We evaluated a combination of finasteride a nd flutamide as potency-sparing androgen ablative therapy (AAT) for ad vanced adenocarcinoma of the prostate. In addition, we evaluated wheth er finasteride provided additional intraprostatic androgen blockade to flutamide. Methods. Twenty men with advanced prostate cancer were giv en flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, fina steride, 5 mg orally every day, was added. PSA values were then measur ed weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehyd roepiandrostenedione (DHEA) levels were measured at baseline and at th e first and second nadir PSA values. Results. The median follow-up per iod was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist t herapy was observed. One patient developed National Cancer Institute g rade 3 diarrhea and was withdrawn from the study. Seven of 20 men deve loped mild gynecomastia, and 5 of 20 developed mild transient liver fu nction test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at ba seline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second P SA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 /- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer foll ow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutam ide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0 .0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was un changed. With the addition of finasteride, testosterone rose another 1 4 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009). Conclusions. Finasteride and fl utamide were safe and well tolerated as AAT for advanced prostate canc er. Finasteride provided additional intraprostatic androgen blockade t o flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduct ion in potency and libido in some patients on longer follow-up. Furthe r evaluation of this therapy is needed. (C) 1997, Elsevier Science Inc .