An international Phase III randomized clinical trial has shown for the first time that the investigational drug cabazitaxel increases survival by 30 percent in men with metastatic prostate cancer that has progressed despite hormone therapy and docetaxel-based chemotherapy, compared with standard therapy.

"There are no effective treatments available to help men with metastatic castration-resistant prostate cancer whose disease continues to grow despite standard chemotherapy, and this large study shows an unequivocal survival benefit for patients who received cabazitaxel," said lead author Oliver Sartor, MD, Piltz Professor for Cancer Research at Tulane Cancer Center. “This agent will provide an important new therapeutic option for men with this advanced form of prostate cancer.”

Therapies that reduce the production of testosterone (a hormone known to fuel prostate cancer growth) are often used to treat advanced prostate cancer. When cancer progresses even in the absence of testosterone, it is called "metastatic castration-resistant prostate cancer" (mCRPC), and is then treated with the chemotherapy drug docetaxel. However, patients eventually become resistant to docetaxel because of a mechanism in prostate cancer cells called the multidrug resistant (MDR) pump, which pumps the anticancer drug out of the cancer cell before it can exert its effects. The MDR pump appears to be unable to recognize cabazitaxel, enabling the drug to enter and effectively kill the prostate cancer cells.

This trial, called the TROPIC study (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated with a Taxotere-Containing Regimen), was conducted at 132 centers in 26 countries and involved 755 men with mCRPC.  Patients were randomly assigned to receive cabazitaxel plus prednisone, or mitoxantrone with prednisone. After a median follow-up of 12.8 months, men in the cabazitaxel group lived a median of 15.1 months, while those in the mitoxantrone group lived 12.7 months -- a difference that was highly statistically significant.

Progression-free survival, tumor response rates, PSA response, and PSA progression all favored the cabazitaxel group; specific data on these endpoints will be presented at the 2010 ASCO Annual Meeting. Men in the cabazitaxel group were more likely than those in the mitoxantrone group to experience fever with declines in white blood cell counts (febrile neutropenia: 7.5 percent versus 1.3 percent, respectively).

Dr. Sartor noted that findings from this study will form the basis of a submission to the U.S. Food and Drug Administration for marketing approval of cabazitaxel. Other studies are being planned to assess the effectiveness of cabazitaxel earlier in the course of prostate cancer treatment, before patients stop responding to docetaxel.