Androgen dynamics and serum PSA in patients treated with abiraterone acetate

Background: We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: COU-AA-30...

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Published in:	Prostate cancer and prostatic diseases Vol. 17; no. 2; pp. 192 - 198
Main Authors:	Ryan, C J, Peng, W, Kheoh, T, Welkowsky, E, Haqq, C M, Chandler, D W, Scher, H I, Molina, A
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-06-2014 Nature Publishing Group
Subjects:	692/53/2422 692/699/67/589/466 692/700/565/1436/1437 Abiraterone Acetate Androgens Androgens - blood Androstenes - therapeutic use Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Double-Blind Method Humans Kallikreins - blood Male Original original-article Prednisone - therapeutic use Properties Prostate cancer Prostate-specific antigen Prostate-Specific Antigen - blood Prostatic Neoplasms, Castration-Resistant - blood Prostatic Neoplasms, Castration-Resistant - drug therapy Testosterone - blood Treatment Outcome
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Summary:	Background: We analyzed the potential of abiraterone acetate (henceforth abiraterone) to reduce androgen levels below lower limits of quantification (LLOQ) and explored the association with changes in PSA decline in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: COU-AA-301 is a 2:1 randomized, double-blind, placebo-controlled study comparing abiraterone (1000 mg q.d.) plus low-dose prednisone (5 mg b.i.d.) with placebo plus prednisone in mCRPC patients post docetaxel. Serum testosterone, androstenedione and dehydroepiandrosterone sulfate from baseline to week 12 were measured by novel ultrasensitive two-dimensional liquid chromatography coupled to tandem mass spectrometry assays in a subset of subjects in each arm (abiraterone plus prednisone, n =80; prednisone, n =38). The association between PSA response (⩽50% baseline) and undetectable androgens (week 12 androgen level below LLOQ) was analyzed using logistic regression. Results: A significantly greater reduction in serum androgens was observed with abiraterone plus prednisone versus prednisone (all P ⩽0.0003), reaching undetectable levels for testosterone (47.2% versus 0%, respectively). A positive association was observed between achieving undetectable serum androgens and PSA decline (testosterone: odds ratio=1.54; 95% confidence interval: 0.546–4.347). Reduction of androgens to undetectable levels did not occur in all patients achieving a PSA response, and a PSA response did not occur in all patients achieving undetectable androgen levels. Conclusions: Abiraterone plus prednisone significantly reduced serum androgens, as measured by ultrasensitive assays and was generally associated with PSA response. However, androgen decline did not uniformly predict PSA decline suggesting ligand-independent or other mechanisms for mCRPC progression.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-News-2 ObjectType-Feature-3 content type line 23
ISSN:	1365-7852 1476-5608
DOI:	10.1038/pcan.2014.8