Influence of prior oral ethinylestradiol use on the efficacy of enzalutamide for the treatment of castration-resistant prostate cancer in men.

OBJECTIVE: To elucidate the effect of prior use of ethinylestradiol on enzalutamide treatment for men with castration-resistant prostate cancer. METHODS: We retrospectively analyzed data from 99 consecutive patients (median age 72 years, range 50-88 years) treated with enzalutamide for castration-resistant prostate cancer between May 2014 and November 2015 after receiving several lines of hormonal therapy. RESULTS: A total of 45 patients were given ethinylestradiol before enzalutamide. The prostate-specific antigen response rate (decline in prostate-specific antigen >50% from baseline) of patients receiving ethinylestradiol and enzalutamide were 51.1% and 41.4%, respectively. Cross-resistance between ethinylestradiol and enzalutamide was clearly observed in the setting of pre-docetaxel. In multivariate analysis, the T stage and number of therapies before enzalutamide were the only significant predictors of prostate-specific antigen response to enzalutamide. However, in patients treated pre-docetaxel use, prior use of ethinylestradiol was a significant predictor of prostate-specific antigen response to enzalutamide, whereas ethinylestradiol did not affect the overall survival of these patients. CONCLUSIONS: Cross-resistance between ethinylestradiol and enzalutamide in the setting of pre-docetaxel therapy seems to be evident. Therefore, ethinylestradiol should be used prudently before enzalutamide in this setting.