Treatment options in castration-resistant prostate cancer: current therapies and emerging docetaxel-based regimens

Abstract

Background: Docetaxel-based chemotherapy remains the standard of care for metastatic castration-resistant prostate cancer (mCRPC) and it is the only globally approved first-line therapy. Although docetaxel offers improved survival for this patient population, it is also associated with toxicity and resistance in many patients, representing a need for more efficacious therapies. Preclinical advances have led to improved understanding of the molecular biology of prostate cancer, and targeted therapies that exploit the signaling pathways and molecular targets that underscore the disease are being clinically investigated in combination with docetaxel.

Design: This article briefly highlights recent data from phase III trials in mCRPC that have led to agent approval. This article also reviews phase II and III trials in which docetaxel-based regimens have been investigated in mCRPC.

Results: Recently approved agents, including sipuleucel-T, cabazitaxel, abiraterone acetate, and enzalutamide, have diversified the mCRPC treatment landscape. Phase III trials evaluating docetaxel in combination with targeted therapies, including potent oral tyrosine kinase inhibitor, dasatinib, in the READY trial and clusterin inhibitor, custirsen, in the SYNERGY trial, are currently ongoing.

Conclusions: In combination with docetaxel, targeted agents dasatinib and custirsen will likely expand the existing treatment paradigm for mCRPC if results from phase III trials are positive.

Keywords: Custirsen; Dasatinib; Docetaxel; Prostate cancer; Review; Targeted therapy.