Improving outcomes with recent advances in chemotherapy for castrate-resistant prostate cancer

The FDA's approval of docetaxel in 2004 created a clear mandate for clinical researchers to create new therapies effective for metastatic castrate-resistant prostate cancer (mCRPC) patients with progression post-docetaxel. In 2010, the first trial to prolong survival in this setting was announced using a cabazitaxel, a novel taxane. This therapeutic agent was specifically designed to have activity in model systems resistant to conventional taxanes. After phase I testing, with observation of clinically significant activity in patients with advanced cancers, cabazitaxel/prednisone was tested in a large phase III trial enrolling patients with mCRPC who had disease progression despite prior docetaxel therapy. This phase III trial TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated With a Taxotere-Containing Regimen), using mitoxantrone/prednisone as a control arm, demonstrated a significant improvement in survival (the primary endpoint). Both subset analyses and secondary endpoints (response rates and time to progression) were supportive of the survival findings. This trial was pivotal for the FDA's approval of the new drug application for cabazitaxel. This review focuses on both the pre-clinical and clinical development of cabazitaxel.