The efficacy of combined androgen blockade therapy consisting of flutamide, a nonsteroidal antiandrogen, plus an LH-RH agonist (F-CAB) was investigated in Japanese patients with untreated advanced prostate cancer (clinical stage D). The primary endpoint was overall survival (OS), while the secondary endpoints were disease-specific survival (DSS), progression- free survival (PFS), reduction of prostate specific antigen (PSA), anti-tumor effects, quality of life (QOL), and adverse drug reactions (ADRs). As of the median observation period of 1,293.5 days, the F-CAB significantly prolonged DSS and PFS relative to LH-RH monotherapy (log rank test: p=0.0343 and 0.0017, respectively). The results of this study indicate the potential of F-CAB as a useful treatment for untreated advanced prostate cancer. Although additional study is considered necessary to determine the daily dosage of flutamide, the anti-tumor effects obtained from this study indicated that 375 mg/day is appropriate as a daily dosage, and 250 mg/day can also be considered when concern exists regarding the occurrence of complications or the development of ADRs, including liver function disorders. [Funded by Nippon Kayaku Co., Ltd., Japic CTI-050101].