Denosumab as a promising novel bone-targeted agent in castration resistant prostate cancer.

Fortunately, more therapeutic progress has been achieved during the last 3 years for patients with castration resistant prostate cancer (CRPC) than during the previous 30 years. During this limited time frame, six compounds (sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223 and enzalutamide, listed in chronologic order) yielded positive results in Phase III trials (Fizazi K. Nonhormone therapy for metastatic castration-resistant prostate cancer. Soc Clin Oncol Educ Book 2013;2013:161-5; Papatsoris AG, Karamouzis MV, Papavassiliou AG. Novel biological agents for the treatment of hormone-refractory prostate cancer (HRPC). Curr Med Chem 2005;12(3):277-96). Regarding skeletal related event (SREs) in patients with CRPC the last 20 years bisphosphonates (i.e., zolendronic acid) were the standard of care until the development of denosumab, which is a novel receptor-activated nuclear factor kappa-β ligand inhibitor. Recent studies demonstrated that denosumab (subcutaneous use) was better than zolendronic acid (intravenous use) for the prevention of SREs and the increase of the bone-metastasis-free survival, while the rate and grade of adverse effects was similar, except for osteonecrosis of the jaw and hypocalcemia. Cost-effectiveness of denosumab is under review in ongoing comparative studies.