Ronald de Wit, MD, PhD, of Erasmus Medical Center, Rotterdam, Netherlands, called the use of docetaxel in addition to androgen-deprivation therapy “the latest paradigm shift” in the treatment of prostate cancer. The data showing a 10% absolute improvement in survival in the metastatic setting “are pretty convincing,” he said.

The greater benefit of docetaxel in hormone-sensitive as compared with castration-resistant disease may be the result of resistant clones or perhaps better exposure to the drug in the hormone-sensitive setting. Docetaxel clearance appears to be greatly increased in castrated men, noted Dr. de Wit.

“We may have underdosed docetaxel in the setting of metastatic castrate-resistant prostate cancer,” he said, adding that he recommends using prednisone with the drug to increase efficacy.

The Lingering Question

According to Dr. de Wit, the “lingering question” is how to optimize the use of the contemporary treatment options in this malignancy, including (along with docetaxel) abiraterone [Zytiga], enzalutamide [Xtandi], and cabazitaxel [Jevtana]. “Learning the optimal sequence of these compounds is important, since the potential overall survival benefit will be smaller with every subsequent line of treatment,” he indicated.

One consideration is the cross-resistance between androgen receptor–targeted agents and by taxanes. Taxanes work, in part, inhibiting androgen receptor nuclear transport and signaling, and their efficacy is affected by prior abiraterone and enzalutamide use, he said.

“The most concern is with the use of these agents pre-docetaxel,” continued Dr. de Wit. “The use of docetaxel in the castrate-sensitive setting, prior to the use of androgen receptor–targeted therapies, might produce a new opportunity.”

 “My conclusion is that men presenting with metastatic prostate cancer who are fit to receive chemotherapy should be offered six cycles of docetaxel plus androgen-deprivation therapy. There is no distinction between high- and low-volume disease. Any metastatic disease by TNM criteria will do,” he said.  ■

Disclosure: Dr. de Wit has served as a consultant or advisor for and has received honoraria from Sanofi, Janssen, Astellas, Roche, and Millennium.