Total androgen blockade: the United States experience

Area of Science:

• Oncology
• Urology

Background:

• Prostate cancer treatment often involves androgen deprivation therapy.
• Maximal androgen blockade (MAB) is a strategy combining LHRH agonists with non-steroidal anti-androgens.
• The effectiveness of MAB in previously untreated, disseminated prostate cancer requires further investigation.

Purpose of the Study:

• To evaluate the efficacy of maximal androgen blockade (MAB) compared to monotherapy with leuprolide in patients with disseminated prostate cancer.
• To assess the impact of adding flutamide to leuprolide on progression-free survival (PFS) and overall survival (OS).

Main Methods:

• A randomized, double-blind trial was conducted involving 603 patients with stage D2 prostate cancer.
• Patients received leuprolide (1 mg/day s.c.) plus either placebo (n=300) or flutamide (250 mg p.o. t.i.d., n=303).
• Progression-free survival and overall survival were the primary endpoints.

Main Results:

• Median PFS was 14 months for leuprolide plus placebo vs. 17 months for leuprolide plus flutamide.
• Median OS was 29 months for leuprolide plus placebo vs. 35 months for leuprolide plus flutamide.
• In patients with minimal disease and good performance status, median PFS was 19 months vs. 48 months, respectively (p=0.035). Flutamide also reduced disease flare.

Conclusions:

• Combined androgen blockade with leuprolide and flutamide demonstrates superior efficacy compared to leuprolide monotherapy in disseminated prostate cancer.
• MAB is particularly beneficial for patients with minimal disease and good performance status.
• The combination therapy offers improved progression-free and overall survival, with reduced side effects like disease flare.