Contemporary agents in the management of metastatic castration-resistant prostate cancer

Abstract

Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC. Cabazitaxel, abiraterone acetate, and enzalutamide are three agents recently approved for the treatment of mCRPC, having shown overall survival benefit in patients previously treated with docetaxel, while both abiraterone acetate and enzalutamide have also shown promise in the pre-docetaxel setting. Sipuleucel-T has shown overall survival benefit in asymptomatic mCRPC, while radium-223 provides survival benefit to patients with mCRPC who are symptomatic from their skeletal metastases in both docetaxel-naïve patients and post-docetaxel patients. Denosumab, an anti-RANKL antibody, has been approved for the prevention of skeletal-related events in patients with prostate cancer bone metastases. This review examines the phase 3 trials supporting the use of theses novel agents in the treatment of mCRPC. While these agents provide incremental increases in patient survival, further study to determine the best choice, combination, and/or sequencing of administration is still necessary.

Economic Outcomes in Patients with Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate Plus Prednisone

“…Docetaxel was the standard of care to treat mCRPC until the introduction of two androgen pathway-targeted treatments, enzalutamide (a second-generation androgen receptor inhibitor) and abiraterone acetate (an irreversible CYP17A1 inhibitor) combined with prednisone (abiraterone). These two agents received US Food and Drug Administration approval for use in mCRPC after docetaxel in August 2012 and April 2011, respectively, and then in chemotherapy-naïve mCRPC in September 2014 and December 2012, respectively [ 9 ]. Enzalutamide and abiraterone have delayed deterioration of health-related quality of life and increased survival for patients with chemotherapy-naïve mCRPC in clinical trial settings [ 10 , 11 ].…”

Evaluation of Small Molecule Drug Uptake in Patient-Derived Prostate Cancer Explants by Mass Spectrometry

“…Enzalutamide (ENZ) is a second-generation AR antagonist with additional modes of action compared to first-generation agents, namely suppression of AR nuclear translocation and binding of the androgen-AR complex to DNA 5 . Enzalutamide is currently used for treatment of metastatic castration resistant prostate cancer (CRPC) 6,7 , and was recently approved for men with high-risk localized disease (HRLD) 3,8,9 . Unfortunately, enzalutamide treatment is not curative, and intrinsic and acquired resistance are both common, representing critical research priorities in the field 3 .…”

Naringin sensitizes human prostate cancer cells to paclitaxel therapy

“… 1 After the development of PCa into CRPC, there are several drugs that prolong life, including taxanes such as paclitaxel, docetaxel, and cabazitaxel and new androgen receptor targeting agents such as abiraterone acetate and enzalutamide. 2 Microtubule-disrupting agents such as taxanes and vinca alkaloids trigger apoptosis by aberrant mitosis or by subsequent multinucleated G1-like state related to mitotic slippage, depends on cell type and drug schedule. 3 Though taxane chemotherapy is standard first-line therapy for recurrent metastatic CRPC, relapse eventually occurs because of the development of drug resistance.…”