Factors predicting efficacy and adverse effects of enzalutamide in Japanese patients with castration-resistant prostate cancer: results of retrospective multi-institutional study.

Abstract

We aimed to evaluate the factors predicting efficacy and adverse effects of enzalutamide in patients with castration-resistant prostate cancer. We retrospectively evaluated data on 345 patients who had received enzalutamide for castration-resistant prostate cancer in 20 hospitals (Kyoto University Hospital and other satellite hospitals). Cox proportional hazards regression analysis was performed to identify factors predicting prostate-specific antigen (PSA) progression after enzalutamide treatment and logistic regression analysis for those associated with development of adverse effects. PSA titers decreased by >50% in 197 patients (57%). The median PSA progression free survival was 163days. Gleason score >8 (HR 2.078, 95% CI 1.37-3.153, P=0.00058), performance status ≥1 (HR 2.292, 95% CI 1.463-3.592, P=0.000296), presence of bone metastasis (HR 1.774, 95% CI 1.019-3.090, P=0.0429), visceral metastasis (HR 2.127, 95% CI 1.215-3.722, P=0.00823), previous steroid treatment (HR 1.780, 95% CI 1.207-2.626, P=0.00361) and docetaxel treatment (HR 1.602, 95% CI 1.051-2.442, P=0.0284) significantly predicted the efficacy of enzalutamide. Adverse effects, including fatigue or appetite loss, occurred in 169 patients (49%), 48 (18%) of whom stopped enzalutamide. Age >75years (HR 1.980, 95% CI 1.270-3.09, P=0.00246) and lower enzalutamide dose (HR 0.437, 95% CI 0.255-1.270, P=0.00249) were significantly associated with development of adverse effects. Enzalutamide treatment is effective in patients with castration-resistant prostate cancer with low Gleason scores, good performance status, without bone or visceral metastasis and no prior steroid or docetaxel treatment. Lower doses of enzalutamide decrease the incidence of adverse effects, especially in older patients.