Leuprolide with and without flutamide in advanced prostate cancer.

Abstract

In a randomized, double-blind trial for metastatic prostate cancer (Stage D2), 603 men received leuprolide, a gonadotropin-releasing hormone analog that inhibits the release of gonadotropins, coupled with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. The 303 men receiving androgen blockade with leuprolide and flutamide demonstrated a longer progression-free survival (16.9 vs. 13.9 months, P = 0.039) and an increased median length of survival (35.0 vs. 27.9 months, P = 0.035). In the subgroup of men with minimal disease and good performance status, the advantages of maximal androgen blockade were more pronounced. It is concluded that combined androgen blockade with leuprolide and flutamide was more effective than leuprolide alone for patients with metastatic cancer of the prostate. The therapeutic benefits, although greatest in patients with minimum disease, need to be evaluated in a prospective, randomized fashion in trials specifically designed for men with minimal disease and good performance status. Exploratory analyses using the black race as an explanatory variable were also performed. Black race is associated with shorter survival times and is also associated with other prognostic factors, including recent weight loss, anemia, elevated phosphatase levels, and pain. These findings suggest the need for future studies of the relationship of black race and response to prostate cancer therapy.