Cross-resistance between Ethinylestradiol and Enzalutamide

[pjoshea13]

New study from Japan.

"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."

-Patrick

ncbi.nlm.nih.gov/pubmed/295...

Int J Urol. 2018 Mar 8. doi: 10.1111/iju.13542. [Epub ahead of print]

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

Hakariya T1, Shida Y1, Tsurusaki T2, Watanabe J3, Furukawa M4, Matsuya F5, Miyata Y1, Sakai H1.

Author information

1

Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

2

Department of Urology, The Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.

3

Department of Urology, Nagasaki Harbor Medical Center, Nagasaki, Japan.

4

Department of Urology, Sasebo City General Hospital, Sasebo, Japan.

5

Department of Urology, National Hospital Organization Nagasaki Medical Center, Omura, Japan.

Abstract

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.

© 2018 The Japanese Urological Association.

KEYWORDS:

castration-resistant prostate cancer; docetaxel; enzalutamide; ethinylestradiol

PMID: 29521011 DOI: 10.1111/iju.13542

[cesanon]

Patrick

My takeaway from this study is that:

1. Maybe you want to avoid estrogen generally

2. But if you are doing Androgen Deprivation Therapy, Estrogen is generally useful.

3. So if you are doing androgen Deprivation Therapy, why not add both Estrogen and Xtandi.

What do you think Patrick?

[pjoshea13 in reply to cesanon]

Very low dose estrogen for bone health while on ADT is not a problem.

Rather, it is estrogen for ADT itself, in the Japanese study.

Seems to me that when we use multiple therapies to go after essentially the same target (androgen receptor), rather than quite independent targets, we invite cross-resistance.

-Patrick

[cesanon in reply to pjoshea13]

Myers original philosophy was to hit once and hit hard to minimize the likelihood of darwinian development of new resistant germ lines.

That philosophy still seems relevant to me.