A study titled “Abiraterone and Increased Survival in Metastatic Prostate Cancer,” published in the May 26 issue of NEJM– New England Journal of Medicine, found that patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel showed a significant improvement in overall survival when treated with abiraterone acetate (Zytiga?, Centocor Ortho Biotech Inc.) plus prednisone compared to patients treated with prednisone plus placebo. The COU-AA-301 study was sponsored by Ortho Biotech Oncology Research & Development, unit of Cougar Biotechnology, Inc.

Results of the pivotal Phase III, randomized, placebo-controlled, multicenter study showed that at pre-specified interim analysis, treatment with abiraterone in combination with prednisone resulted in a 35.4% reduction in the risk of death (14.8 months vs. 10.9 months [hazard ratio (HR) = 0.65; 95% CI: 0.54, 0.77; p<0.001]) and a 3.9 month difference in median survival compared to placebo plus prednisone.

The most common adverse events identified by the authors were fatigue, back pain, nausea, constipation, bone pain and arthralgia, which occurred at similar frequency in both arms. Urinary tract infections were more frequent in the abiraterone arm. Adverse events associated with elevated mineralocorticoid levels due to CYP17 inhibition (fluid retention and edema, hypokalemia and hypertension), as well as cardiac disorders and liver-function test abnormalities were deemed of special interest and were more common in the abiraterone arm.

“Given that men with metastatic castration-resistant prostate cancer have few options, we are pleased with the results of this rigorous study, which show that abiraterone acetate may extend survival in these patients,” said Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute for Cancer Research, The Royal Marsden NHS Foundation Trust, and lead author. “The data indicate that abiraterone acetate has the potential to meet a significant unmet need for these patients.”

Androgens are hormones that promote the development and maintenance of male sex characteristics. However, in prostate cancer, androgens can help fuel the tumor’s growth. Androgen production primarily occurs in the testes and adrenal glands; in men with prostate cancer, the tumor tissue is an additional source of androgens. Abiraterone is an oral androgen biosynthesis inhibitor that works by selectively inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.

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The U.S. Food and Drug Administration (FDA) approved abiraterone on April 28, 2011 for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.

The results of this randomized, double-blind, placebo-controlled study were presented in part during a late-breaking presentation at the Presidential Symposium at the 35th Annual European Society for Medical Oncology Congress in Milan, Italy on October 11, 2010, and have been presented at several conferences since then.

Study Design
Abiraterone, in combination with prednisone, was evaluated in a Phase 3, randomized, placebo-controlled, multicenter clinical study in patients who had received prior chemotherapy containing a taxane (N = 1,195). A total of 1,195 patients were randomized 2:1 to receive abiraterone 1000 milligrams (mg) daily in combination with prednisone 5 mg twice daily or placebo in combination with prednisone 5 mg twice daily (control arm). The primary endpoint was overall survival.

For more information:
– De Bono JS, Logothetis CJ, Molina A,et al. Abiraterone and Increased Survival in Metastatic Prostate Cancer. N Engl J Med 364;21, 1995 -2005.
– Antonarakis ES, Eisenberger MA. Expanding Treatment Options for Metastatic Prostate Cancer N Engl J Med 2011; 364:2055-2058May 26, 2011
Clinical Trial: Abiraterone Acetate in Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy

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