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

To elucidate the effect of prior use of ethinylestradiol on enzalutamide treatment for men with castration-resistant prostate cancer.

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.

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.

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.

International journal of urology : official journal of the Japanese Urological Association. 2018 Mar 08 [Epub ahead of print]

Tomoaki Hakariya, Yohei Shida, Toshifumi Tsurusaki, Junichi Watanabe, Masataka Furukawa, Fukuzo Matsuya, Yasuyoshi Miyata, Hideki Sakai

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Department of Urology, The Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan., Department of Urology, Nagasaki Harbor Medical Center, Nagasaki, Japan., Department of Urology, Sasebo City General Hospital, Sasebo, Japan., Department of Urology, National Hospital Organization Nagasaki Medical Center, Omura, Japan.