Cabazitaxel

Abstract

Prostate cancer is the most common cancer in men in the United States excluding skin cancer. Androgen deprivation therapy is initially effective for most patients with metastatic prostate cancer; however, castration-resistant prostate cancer (CRPC) usually develops when disease progresses despite conventional hormone therapies. There are few treatment options for progressive CRPC. Until recently, only one treatment, docetaxel, had been shown to prolong survival, and no agents had been shown to improve survival in docetaxel-refractory disease. This changed in June 2010 with the U.S. Food and Drug Administration approval of cabazitaxel. Cabazitaxel is a new option for patients with CRPC whose disease progresses during or after docetaxel treatment (docetaxel refractory). Cabazitaxel is a novel taxane that has been shown to have poor affinity for the p-glycoprotein drug efflux pump, a major mechanism of resistance to docetaxel. In combination with prednisone, cabazitaxel was shown to significantly prolong overall survival by 2.4 months when compared with mitoxantrone in a large randomized phase III trial in metastatic CRPC patients previously treated with first-line docetaxel. The most common toxicities with cabazitaxel are neutropenia (88%), anemia (81%), thrombocytopenia (43%), fatigue (27%), nausea (23%), and diarrhea (11%). This review will examine the clinical development, efficacy, adverse effects, and suggested monitoring for this new agent. The combination of cabazitaxel and prednisone is an important new treatment option for men with docetaxel-refractory metastatic CRPC. However, this agent should be administered with close, appropriate monitoring, especially in men at high risk of neutropenia or diarrhea. Future research directions for this new agent will include exploring its role in combination with other agents and comparing with docetaxel for the first-line treatment of metastatic CRPC.