Rationale for Targeting Androgen Receptor Overexpression in Bladder Cancer

Shilpa Gupta, MD, associate professor of Genitourinary Oncology at the Cleveland Clinic, explains the rationale for adding androgen receptor (AR) therapy to cisplatin- and gemcitabine-based chemotherapy.

AR is overexpressed in bladder cancer, and preclinical studies have shown that AR is a good target to inhibit when treating patients with bladder cancer. Specifically, AR inhibitors prevent tumor growth and disease progression. There is also research that shows that AR is sensitive to cisplatin, according to Gupta. These early studies served as the rationale for a study in which enzalutamide (Xtandi) was added to cisplatin and gemcitabine.

Aphase I study was conducted with the combination of enzalutamide plus cisplatin and gemcitabine. In the dose-finding portion of the study, patients received either enzalutamide 80mg or 160mg along with the standard doses of cisplatin and gemcitabine.

No dose-limiting toxicities were observed in the dose-finding portion, and the study moved on to the dose-expansion phase.