**2. Cabazitaxel**

Cabazitaxel is a new semi-synthetic derivative of the taxoid 10-deacetylbaccatin-III, which like docetaxel binds to and stabilizes tubulin. But, unlike docetaxel is a poor substrate for the P-glycoprotein drug efflux pump and may also have enhanced penetration through the blood-brain barrier (Niraula and Tannock, 2011). In a Phase 1 trial of cabazitaxel the dose limiting toxicity at 25 mg/m2 every 3 weeks was grade 4 neutropenia, and the common non-hematologic adverse events included low grade diarrhea (52%), nausea (40%) and vomiting (16%). Two patients with CRPC, including one previously treated with docetaxel showed a partial response (Mita *et al.*, 2009).

A phase III multicenter, multinational trial comparing cabazitaxel with mitoxantrone in the second line setting was conducted with a primary endpoint of overall survival (OS) (de Bono*,* 2010). Cabazitaxel significantly improved median OS compared with mitoxantrone (15.1 months vs 12.7 months, respectively; HR 0.72; 95% CI 0.61-0.84; p<0.0001). Secondary endpoints including progression free survival (PFS) (2.8 months vs 1.4 months), response rate (14.4% vs 4.4%; p=0.005), and median time to progression (TTP) by tumor assessment (8.8 months vs. 5.4 months; p<0.0001) also favored cabazitaxel. From a toxicity standpoint febrile neutropenia, neutropenia, leukopenia and diarrhea were more common in the cabazitaxel arm. One major concern with cabazitaxel however was a toxic death rate of 5% compared to only 1.9% for mitoxantrone. As cabazitaxel moves out of the controlled clinical trial setting into general use, early and proactive management of the toxicites will be critical. Cabazitaxel was FDA approved in 2010 for patients progressing on or after docetaxel. In the same year, a second drug, Abiraterone was also approved for use in the post-docetaxel setting.
