Metabolic and toxicological considerations of newly approved prostate cancer drugs

Despite increasing early detection and treatment of prostate cancer, a subset of patients presents with or develops metastatic disease. Androgen deprivation therapy is effective but resistance eventually develops, resulting in a lethal phenotype known as castration-resistant prostate cancer (CRPC). Recently, several novel treatments, each with distinct mechanisms of actions, have been approved for the treatment of CRPC. Understanding of the metabolic and toxicological considerations of each treatment is crucial to the successful management of patients with this lethal disease.

The present review focuses on the metabolism and toxicology characteristics of recently approved therapies in the treatment of metastatic CRPC. Specifically, the authors review the mechanism of action of these therapies in addition to their, efficacy and usage recommendations for hepatic and renal impairment. The authors, furthermore, also consider their adverse effect profile.

Despite the expanding armamentarium of effective treatments for CRPC, the exact choice, timing and sequence of various therapies remains an inexact science and requires further investigation. Variations in patient comorbidities, disease burden, organ functions and adverse events are all critical determinants in selection of treatment. Identification and validation of molecular pathways and specific targets that drives disease progression will be critical in the continued development of effective treatments in advanced prostate cancer.