Emerging novel therapies for advanced prostate cancer.

This review examines the development and efficacy of novel treatment options for advanced prostate cancer and discusses novel therapies that are on the horizon. Since the introduction of docetaxel as the standard treatment for patients with metastatic castration-resistant prostate cancer (CRPC), a number of different agents have been tested but failed to demonstrate improvement in overall survival (OS). Recently, three novel compounds have demonstrated OS benefit and one other showed reduction in skeletal-related events (SREs). Sipuleucel-T, a novel vaccine, was approved by the US regulatory authorities in April 2010 for patients with early advanced prostate cancer. A new taxane, cabazitaxel, and abiraterone acetate, an androgen biosynthesis inhibitor, have shown an OS benefit in advanced CRPC after docetaxel, leading to drug approval. A new bone-targeting agent, denosumab, a receptor activator of nuclear factor κB ligand (RANKL) antagonist, showed a modest reduction in SREs in comparison to zoledronic acid in patients with bone metastases. Other promising novel agents are currently being tested in the clinical setting of advanced CRPC. These include, androgen receptor inhibitors (MDV3100), androgen biosynthesis inhibitors, angiogenesis inhibitors (thalidomide, lenalidomine, aflibercept, tasquinimod), a novel form of radiotherapy (radium-223), and immune-modulating compounds (PROSTVAC-VF). Improvements in progression-free survival and OS rates, observed with novel agents, in metastatic prostate cancer have led to a shift in treatment paradigm. The challenge will be to position the current established and expected novel treatments in the new landscape of metastatic prostate cancer and to determine at what point and time in the disease course they can best be administered.