Chemotherapy and Androgen Receptor-Directed Treatment of Castration Resistant Metastatic Prostate Cancer

Metastatic castration-resistant prostate cancer (mCRPC) remains incurable despite development of effective treatment. Since 2004, docetaxel every 3 weeks plus continuous prednisone has been standard first-line chemotherapy in castration-resistant prostate cancer (CRPC) based on improved survival compared with the previous standard regimen, mitoxantrone plus prednisone. Subsequently, various randomized phase III trials have been performed investigating whether the docetaxel combined with various targeted agents had superior clinical outcome as compared to docetaxel alone. Combinations with agents, such as bevacizumab, dasatinib, and atrasentan, expected to be promising based on their mode of action and/or additive or synergistic activity in preclinical studies, all failed to further improve outcomes or were proven to have a detrimental effect. A PARP inhibitor has been shown to be effective in prostate cancer patients with tumors exhibiting defects in DNA repair genes.