critical appraisal of cabazitaxel in the management of advanced prostate cancer

Sumanta Kumar Pal1, Przemyslaw Twardowski1, Oliver Sartor21Division of Genitourinary Malignancies, Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Los Angeles, CA, USA; 2Departments of Urology and Medicine, Tulane University School of Medicine, New Orleans, LA, USAAbstract: Docetaxel remains a cornerstone of therapy for the patient with metastatic castration-resistant prostate cancer (CRPC). However, the landscape of CRPC therapy is changing rapidly – recently, data from the phase III TROPIC study revealed a survival advantage with the novel taxane cabazitaxel/prednisone (compared with mitoxantrone/prednisone) in a cohort of 755 men with docetaxel-refractory metastatic CRPC. Interestingly, cabazitaxel bears substantial structural similiarity to docetaxel but appears to be mechanistically distinct. In preclinical studies, the agent has antitumor activity in a variety of docetaxel-refractory in vitro and in vivo models. Subsequent to phase I testing in advanced solid tumors (where neutropenia was identified as a dose-limiting toxicity), the agent was assessed in a phase II trial in advanced, taxane-refractory breast cancer and in the aforementioned phase III TROPIC study. This review describes in detail the preclinical and clinical development of cabazitaxel.Keywords: cabazitaxel, castration resistant prostate cancer, Jevtana, breast cancer, taxane