Carbazitaxel extends survival in Taxotere-refractory patients with CRPC
Posted Mar 04 2010 12:00am
According to a media release from Sanofi-Aventis early this morning, the second-generation taxane carbazitaxel, when given in combination with prednisone, is capable of extending median survival by 2.4 months compared to mitoxantrone + prednisone in prostate cancer patients who are refractory to docetaxel (Taxotere) chemotherapy. The full details of the TROPIC study (a randomized, double-blind trial involving over 700 patients) will be presented tomorrow at the GU Oncology Symposium in San Francisco.
Eligible patients had to have metastatic, hormone-refractory prostate cancer, and have progressive disease following chemotherapy with docetaxel + prednisone.
The trial enrolled 755 patients, of whom 378 were randomized to receive carbazitaxel + prenisone (or prednisolone) and 377 to mitoxantrone + prednisone (or prednisolone).
Patients could be treated for up to 10 cycles of therapy with either of the two drug combinations.
Carbazitaxel + prednisone reduced the overall risk of death by 30 percent compared to mitoxantrone + prednisone in these patients.
Median overall survival of patients on the carbitaxel arm of the trial was 15.1 months.
Median overall survival on the mitoxantrone arm was 12.7 months.
A significant risk for side effects was observed among patienst receiving carbitaxel, including grade 3/4 febrile neutropenia in 81.7 percent of patients and infections in 10.2 percent.
4.9 percent of the deaths in the carbitaxel arm of the trial were specifically associated with adverse events (as compared to 1.9 percent of deaths in the mitoxantrone arm).
It is clear that carbatexel is effective in the treatment of patients with very late stage hormone refractory prostate cancer, although it also appears to have a significant range of side effects in these patients. The question still to be answered is whether carbitaxel, if given earlier in the disease process, instead of docetaxel, would be able to extend survival longer than the 2 months originally demonstrated in the docetaxel clinical trials, and with a lower incidence of adverse events.
We understand that Sanofi-Aventis has already started the process of submission of data to regulatory authorities to seek approval to market carbazitaxel for the treatment of prostate cancer patients refractory to docetaxel. In the U.S., the Food and Drug Administration has “fast-tracked” this New Drug Application (NDA).