Maximum androgen-blockade with medical or surgical castration in advanced prostate cancer: A meta-analysis of nine published randomized controlled trials and 4128 patients using flutamide

Abstract

With the recent Southwest Oncology Group (SWOG) publication of their metastatic prostate cancer clinical trial results, which concluded that orchiectomy and flutamide as maximal androgen blockade (MAB) therapy vs orchiectomy alone does not significantly improve survival (NCI 0105), and the 1989 publication from the same cooperative group indicating a 24% improvement in survival for MAB therapy with leuprolide and flutamide versus leuprolide alone (NCI 0036), clinicians may well be undecided about the likelihood of clinical benefits with flutamide in combination with medical or surgical castration. To better characterize this important therapeutic decision, we assessed the survival benefit of MAB therapy with flutamide through a meta-analysis of up-to-date information from studies reported/conducted from 1989 through 1998. All peer-reviewed published randomized controlled trials comparing treatment with flutamide plus either lutenizing hormone releasing hormone (LhRH) agonists or orchiectomy as MAB treatment with LhRH or orchiectomy alone were included. The primary objective of the study was to form a combined estimate and confidence interval for the hazard ratio (as measured by the relative risk (RR) of survival in a comparison of castration vs MAB) summarizing the effect of flutamide treatment on overall survival. Directly extracted estimates of the log hazard ratio were used if available (1 study); if not, either an estimate of the RR based on a reported P-value from a log rank test (7 studies) or a discrete proportional hazards approximation based on reconstructed annual life tables for the treatment arms (1 study) were used. Nine studies with 4128 patients with advanced prostate cancer were included in these analyses. Pooled estimates demonstrated a 10% improvement in overall survival with flutamide as MAB therapy (relative risk (RR)=0.90, 95% Confidence Interval=0.79, 1.00). The currently available updated evidence from randomized trials shows a 10% benefit in overall survival with flutamide as MAB therapy in comparison to conventional castration, almost identical to the estimate reported in the recently published Southwest Oncology Group Study (NCI 0105).