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

With the recent Southwest Oncology Group (SWOG) publication of their metast atic prostate cancer clinical trial results, which concluded that orchiecto my and flutamide as maximal androgen blockade (MAB) therapy vs orchiectomy alone does not significantly improve survival (NCI 0105), and the 1989 publ ication from the same cooperative group indicating a 24% improvement in sur vival for MAB therapy with leuprolide and flutamide versus leuprolide alone (NCI 0036), clinicians may well be undecided about the likelihood of clini cal benefits with flutamide in combination with medical or surgical castrat ion. To better characterize this important therapeutic decision, we assesse d the survival benefit of MAB therapy with flutamide through a meta-analysi s of up-to-date information from studies reported/conducted from 1989 throu gh 1998. All peer-reviewed published randomized controlled trials comparing treatmen t with flutamide plus either lutenizing hormone releasing hormone (LhRH) ag onists or orchiectomy as MAB treatment with LhRH or orchiectomy alone were included. The primary objective of the study was to form a combined estimat e and confidence interval for the hazard ratio (as measured by the relative risk (RR) of survival in a comparison of castration vs MAB) summarizing th e effect of flutamide treatment on overall survival. Directly extracted est imates of the log hazard ratio were used if available (1 study); if not, ei ther 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 reco nstructed 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 over all survival with flutamide as MAB therapy (relative risk (RR)= 0.90, 95% C onfidence 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).