In April 2011, the FDA approved the androgen synthesis inhibitor abiraterone acetate in combination with low-dose prednisone for the treatment of patients with metastatic CRPC who had previously received a docetaxel-containing chemotherapy regimen. Many patients are known to have enhanced synthesis of autocrine and/or paracrine androgens in their tumor microenvironment during ADT treatment, and abiraterone acetate inhibits one of the key enzymes, cytochrome P450c17 (lyase, hydroxylase), which metabolizes smaller amounts of the androgen testosterone/dihydrotestosterone from the adrenal glands. FDA approval was based on the results of a phase III randomized placebo-controlled clinical trial in patients with metastatic CRPC who had previously received a docetaxel-containing regimen. Patients were randomized to receive once-daily oral abiraterone acetate 1000 mg (N=797) or once-daily placebo (N=398), and both groups received prednisone daily. The trial was unblinded when patients receiving abiraterone acetate were shown to have achieved a statistically significant improvement in overall survival (OS) at the scheduled midpoint. Median survival was 14.8 months and 10.9 months in the abiraterone and placebo groups, respectively (HR 0.646; 95% CI, 0.54-0.77; P<0.0001). Time to onset of imaging progression (5.6:3.6 months), PSA reduction (29%:6%), and pain relief (44%:27%) also improved with abiraterone acetate treatment. The most common adverse reactions (>5%) with abiraterone acetate/prednisone were joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flashes, diarrhea, urinary tract infection, cough, hypertension, cardiac arrhythmia, dysuria, nocturia, dyspepsia, or upper respiratory tract infection. The most common adverse drug reactions leading to discontinuation included elevated levels of glutamic aminotransferase and/or glutamic aminotransferase, urinary sepsis, or heart failure (all seen in <1% of patients on abiraterone). The most common electrolyte imbalances in patients treated with abiraterone were hypokalemia (28%) and hypophosphatemia (24%).