Enzalutamide, a Second Generation Androgen Receptor Antagonist: Development and Clinical Applications in Prostate Cancer

Enzalutamide, formerly known as MDV3100, is an oral second generation androgen receptor (AR) inhibitor that was chosen from a screen of agents and shown in preclinical studies to have greater affinity for the AR than its predecessors without any agonistic effects. The pre-clinical work that led to the interest in studying this agent and the history of the clinical development of enzalutamide from first in man phase 1 through phase 3 and regulatory approval are reviewed. Information about the toxicity profile and prescribing enzalutamide are discussed in detail. The availability of enzalutamide is put into context with the five other agents that modify survival outcomes in metastatic castration resistant prostate cancer. Some of the new challenges confronting the field regarding sequencing and combinations of these agents and the potential for a change in the natural history of the disease, are also discussed.