A Controlled Trial of Leuprolide with and without Flutamide in Prostatic Carcinoma

To test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer, we conducted a randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D₂). All 603 men received leuprolide, an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins, in combination with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. As compared with the 300 patients receiving leuprolide and placebo, the 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival (16.5 vs. 13.9 months; P = 0.039) and an increase in the median length of survival (35.6 vs. 28.3 months; P = 0.035). The differences between the treatments were particularly evident for men with minimal disease and good performance status; however, further studies should be conducted in this subgroup. Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade, when leuprolide alone often produces a painful flare in the disease. We conclude that in patients with advanced prostate cancer, treatment with leuprolide and flutamide is superior to treatment with leuprolide alone. FOR many years, the growth of prostatic cancer cells has been known to be hormone dependent. Various therapeutic maneuvers designed to interfere with androgen-induced stimulation of tumor growth have been shown to modify the biologic behavior of this neoplasm, resulting in some of the most effective systemic palliative treatments known for metastatic cancer.^{1 2 3 4 5} Widely applied methods of treatment focus on the elimination or reduction of androgens of gonadal origin by surgical castration, administration of pharmacologic doses of estrogens, or more recently, inhibition of the synthesis and release of gonadotropins by the pituitary with the use of potent analogues of gonadotropin-releasing…