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Int. J. Radiat. Oncol. Biol. Phys. · Jun 2015
External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens.
- Eunpi Cho, Elahe A Mostaghel, Kenneth J Russell, Jay J Liao, Mark A Konodi, Brenda F Kurland, Brett T Marck, Alvin M Matsumoto, Bruce L Dalkin, and R Bruce Montgomery.
- University of Washington School of Medicine, Seattle, Washington; Fred Hutchinson Cancer Research Center, Seattle, Washington.
- Int. J. Radiat. Oncol. Biol. Phys. 2015 Jun 1; 92 (2): 236-43.
PurposeOptimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression.Methods And MaterialsA prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry.ResultsA total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse.ConclusionsAddition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.Copyright © 2015 Elsevier Inc. All rights reserved.
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