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Adding abiraterone improves suppression of intraprostate androgens

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What this therapy failed to do

The study by Taplin et al demonstrates that targeting androgen receptors in the preprostatectomy setting with abiraterone has a clear biologic effect, decreasing tissue levels of androgens. But this effect hasn’t yet been shown to translate into clinical benefit, and cannot be considered a standard of care.

One of the most striking findings is what this neoadjuvant therapy did not accomplish: It didn’t eradicate the cancer. Many patients showed residual cancer in specimens taken at subsequent prostatectomy: 54% had a pathologic stage of T3 or higher, 18% had positive lymph nodes, 14% had positive margins, and the pathologic complete response rate was only 7%.

Eric J. Small, M.D., is at the University of California, San Francisco. He has received research funding from Janssen Oncology and Dendreon and has served as a consultant to Kite Pharma. Dr. Small made these remarks in an editorial accompanying Dr. Taplin’s report (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2014.57.8534]).


 

References

Adding abiraterone to standard neoadjuvant therapy using luteinizing hormone-releasing hormone agonists induces markedly more effective androgen suppression within the prostate tissue in men who have high-risk localized prostate cancer, according to a report published online Oct. 13 in the Journal of Clinical Oncology.

Patients with localized high-risk prostate cancer show the highest recurrence rates after prostatectomy, with PSA relapse ranging from 40% to 65%. Abiraterone intensifies androgen deprivation therapy because it inhibits all sources of androgens: testicular, adrenal, prostate, and (presumably) tumor, said Dr. Mary-Ellen Taplin of the Dana-Farber Cancer Institute, Boston, and her associates.

In an open-label phase II clinical trial, Dr. Taplin and colleagues assessed 58 men who had localized prostate cancer plus PSA levels above 10 ng/ml, a PSA velocity greater than 2 ng/ml during the preceding year, and/or a Gleason score of 7 or higher. These participants were randomly assigned to receive 12 weeks of either LHRH agonists alone (28 men) or LHRH agonists plus abiraterone (30 men) in the randomized portion of the study. Then participants who had not received the abiraterone crossed over, and all the participants received another 12 weeks of abiraterone before undergoing prostatectomy (J. Clin. Oncol. 2014 October 13 [doi:10.1200/JCO.2013.53.4578]).

In biopsies taken at 12 weeks, the addition of abiraterone reduced median levels of testosterone within the prostate by 37% and reduced median levels of dihydrotestosterone by 86%. Further study is needed to determine whether this laboratory response indicating reduced tumor burden translates into a clinical response of improved survival or quality of life, Dr. Taplin and her associates said.

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