Enhancement of intermittent androgen ablation by off-cycle maintenance with finasteride in LNCaP prostate cancer xenograft model

BACKGROUND. Intermittent androgen ablation (IAA) was developed with the intention of delaying progression of prostate cancer to androgen-independence and improving quality of life. Our previous studies suggest that relative to dihydrotestosterone (DHT), testosterone (T) is a weak inducer of proliferation and a more potent inducer of differentiation. We hypothesize that administration of finasteride (F), a type-II 5-alpha-reductase inhibitor that increases T and decreases DHT, during the IAA off-cycle would enhance the efficacy. METHODS. After LNCaP tumor establishment, nude mice were castrated and randomized to continuous androgen ablation (CAA), continuous androgen ablation plus finasteride (CAA+F), intermittent androgen ablation (IAA), or intermittent androgen ablation plus finasteride (IAA + F). RESULTS. After one cycle of therapy, mice treated with IAA + F had significantly less tumor growth than the other treatment groups (P = 0.002). Mice treated with IAA + F had the best survival (P = 0.048) and were 3-5 times more likely to be alive 70 days following treatment initiation. CONCLUSIONS. IAA with finasteride provides the most favorable tumor growth kinetics and survival compared to both CAA and standard IAA. Prostate 66: 495-502, 2006. (c) 2005 Wiley-Liss, Inc.