Dr. Petrylak on Orteronel Plus Docetaxel in Prostate Cancer

Daniel P. Petrylak, MD, director, Prostate and Genitourinary Cancer Program, co-director, Signal Transduction Research Program, at the Smilow Cancer Center at Yale-New Haven, describes a phase I/II study examining the safety and efficacy of orteronel (TAK-700) in combination with docetaxel and prednisone in metastatic castration-resistant prostate cancer (mCRPC).

The varying mechanisms of actions for these agents provided the rationale behind the combination, Petrylak explains. In general, the depletion of testosterone levels with orteronel, an investigational nonsteroidal 17,20-lyase inhibitor, has a synergistic affect in mCRPC when combined with microtubule inhibitors, like docetaxel, which may inhibit androgen receptor translocation.

Overall, the trial found that full doses of each agent (orteronel at 400 mg BID and 75 mg/m² q3w) could be administered safely over the course of the trial. Additionally, the combination resulted in a strong PSA response, including a 50% drop in PSA for 80% of patients, Petrylak notes. The next steps for this combination remain unclear, since trials examining docetaxel in combinations have been disappointing. However, Petrylak feels that orteronel may be the optimal agent for this combination.