A randomized phase II study comparing bipolar androgen therapy vs. enzalutamide in asymptomatic men with castration resistant metastatic prostate cancer: The TRANSFORMER trial.

TPS5079 Background: Prostate cancer can progress despite androgen deprivation therapy through overexpression of the androgen receptor (AR) and expression of AR splice variants. Almost paradoxically, testosterone given to cancer cells in this state can cause growth inhibition. The AR is normally degraded during progression through the cell cycle, but androgen-bound AR is stabilized, thus arresting the cell cycle and inducing DNA strand breaks through interaction with topoisomerase-IIb. Clinically, supraphysiologic testosterone given to men with castration-resistant prostate cancer was found to be safe in a pilot clinical trial, producing responses and re-sensitizing patients to subsequent anti-androgen therapy. In this context, we designed a randomized phase II study comparing bipolar androgen therapy (BAT) to enzalutamide for patients who have experienced progression on abiraterone. Methods: In this multi-center randomized study, funded by a grant from the Department of Defense, eligible patients have asy...