Novel agents for the management of castration-resistant prostate cancer

Abstract

Over the past 2 years, four new treatments have entered the treatment armamentarium for patients with castration-resistant prostate cancer (CRPC). Although these novel agents differ in their mechanism of action, they all face the same challenges: patient selection, timing of therapy and the cost/benefit of their use. In this review, we will discuss their development and implications when selecting treatment options for CRPC patients. Over the past few years, a better understanding of the biology of CRPC has allowed us to develop rational therapies that have resulted in an improvement in the outcome of prostate cancer patients. Immunotherapy has entered the field and despite its limitations and challenges is here to stay. A better understanding of the long-term complications of androgen deprivation has changed the initial approach to most patients with advanced disease, and bone health has become a major focus in their management. Understanding the importance of the androgen receptor and other ligands has led to a dramatic paradigm shift in the treatment of patients with metastatic disease in which the androgen receptor becomes a central therapeutic target in the disease. Specific adrenal inhibitors and engineered super androgen receptor inhibitors have become the most promising agents in the disease. Similarly, chemotherapy has demonstrated clinical benefit and is now a standard of care in docetaxel-refractory patients. The management of CRPC patients continues to evolve. Novel treatments recently approved by the US Food and Drug Administration have significantly impacted the outcome of CRPC. With the economic impact of their use, selecting the right patient, defining the appropriate timing and sequence of therapy have become critical facts that need to be followed when defining the contemporary treatment options for men with CRPC.