To address the need for better therapies for men with high-risk localized prostate cancer, Dr. Mary-Ellen Taplin of the Dana-Farber Cancer Institute led a multicenter PCCTC clinical trial to test the hypothesis that intense androgen-deprivation therapy (ADT), a luteinizing hormone-releasing hormone agonist (LHRHa) combined with abiraterone acetate (Zytiga) before prostatectomy, can improve survival. This comprehensive approach to suppressing tissue androgens – using a LHRHa to target testosterone production induced by the pituitary gland and abiraterone acetate to inhibit a key enzyme involved with testosterone production in testicular, adrenal and prostatic tumor tissues – was tested in a phase II trial designed to demonstrate the impact of treatment on tissue androgen levels.
The trial enrolled 58 patients with localized high-risk prostate cancer randomized to receive LHRHa or LHRHa plus abiraterone for 12 weeks at which point biopsy studies were conducted to measure tissue androgen levels. All patients continued with 12 additional weeks of LHRHa plus abiraterone followed by prostatectomy. The addition of abiraterone acetate to LHRHa resulted in dramatic declines in key androgens including DHT (85%), DHEA (97%-98%), androstenedione (77%-78%) and testosterone (38%) when compared to LHRHa alone (p < 0.001 all measures save for testosterone, p < 0.05). As circulating androgen levels closely correlate with tumor burden, these results suggest intense ADT represents a promising neoadjuvant approach to more completely controlling prostate cancer.
The full report will be published in the Journal of Clinical Oncology.
Taplin M-E, Montgomery B, Logothetis CJ, et al: Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: Results of a randomized phase II neoadjuvant study. J Clin Oncol doi: 10.1200/JCO.2013.53.4578