European Urology

deBono JS, Logothetis CJ, Molina A, et al
N Engl J Med 2011;364:1995–2005
Expert's summary:
This study randomized 1195 patients with disease progression after taxotere chemotherapy for prostate cancer to receive abiraterone plus prednisone or placebo plus prednisone. In a well-balanced randomized group, with median follow-up of 13 mo, overall survival was increased significantly with abiraterone (14.8 mo vs 10.9 mo). Secondary end points such as time to prostate-specific antigen (PSA) progression, progression-free survival, and PSA response were also significantly improved with abiraterone. Side effects such as fluid retention, hypertension, and hypokalemia were more frequently seen in the abiraterone group than the placebo group.
Expert's comments:
Prostate cancer is generally considered to be a hormonally sensitive disease, but patients ultimately fail first- or second-line hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists and antiandrogens. Some centers have utilized second-line chemotherapy with CYP-17 inhibitors such as ketoconazole or aminoglutethamide with modest responses. Patients who fail this therapy generally receive chemotherapy with docetaxel.

This important study highlights that many patients with metastatic prostate cancer are not castration resistant. These studies confirm that the androgen receptor can still respond to miniscule levels of androgen. This study with abiraterone provides evidence that despite treatment with medical castration, sufficient levels of androgen exist to continue tumor growth. Although an LHRH analog with or without antiandrogen suppresses testosterone to the range of 20–50 ng/dl, abiraterone suppresses levels to the range of 1–2 ng/dl.

The impressive response rate to abiraterone plus prednisone was noted in all subcategories, including patients with several previous chemotherapy regimens, older patients, patients with visceral disease, and patients with baseline PSA above median. Although abiraterone plus prednisone has been approved by the US Food and Drug Administration for patients who have failed taxotere chemotherapy, additional studies will be necessary to identify its proper place in the armamentarium of treatment for prostate cancer.

Conflicts of interest

The author has nothing to disclose.