Cabazitaxel improves survival of docetaxel-resistant prostate cancer

NEW YORK (Reuters Health) - Cabazitaxel, a new taxane agent, offers better survival than mitoxantrone when castration-resistant prostate cancer progresses despite docetaxel treatment, new research shows.

With cabazitaxel on board, overall survival improved by 30% and median survival climbed from 12.7 to 15.1 months, according to the researchers. They presented the data - from the international phase III TROPIC trial -- in San Francisco this week at the third annual Genitourinary Cancers Symposium.

"These results are significant because they demonstrate a survival advantage with a new agent for patients with prostate cancer who have no standard option today," lead researcher Dr. A. Oliver Sartor, from Tulane Cancer Center, New Orleans, told Reuters Health.

Advanced prostate cancer is typically treated with medical or surgical castration to reduce the stimulatory effects of testosterone on cancer cells. When this treatment fails, patients receive docetaxel, but unfortunately, the cancer cells can develop a pump that removes docetaxel from the cell, rendering it ineffective.

There is an unmet need for agents that can help when disease progresses on docetaxel, Dr. Sartor said. Cabazitaxel could be effective in such cases, since the cancer cell pump that removes docetaxel appears unable to recognize and eliminate cabazitaxel.

In TROPIC, 755 patients with disease progression during or after docetaxel therapy were randomized to receive cabazitaxel (25 mg/m2) or mitoxantrone (12 mg/m2) every 3 weeks in combination with prednisone (10 mg/day).

Dr. Sartor said mitoxantrone was selected as a comparator agent because it has shown some efficacy against metastatic castration-resistant prostate cancer and because of its use in other randomized trials.

The cabazitaxel group received a median of 6 treatment cycles, and the mitoxantrone group received a median of 4 cycles.

With a median follow-up of 12.8 months, cabazitaxel was associated with significantly longer overall survival on intent-to-treat analysis (HR, 0.70; p < 0.0001). Cabazitaxel also provided significantly higher progression-free survival and tumor response rates.

Neutropenia, the most common grade 3/4 side effect, occurred in 81.7% of cabazitaxel patients and 58.0% of mitoxantrone patients. Febrile neutropenia occurred in 7.5% and 1.3%, respectively.

TROPIC was funded by Sanofi-Aventis, which is seeking marketing approval for cabazitaxel from the US Food and Drug Administration.

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