PURPOSE: @entity1 previously treated with @entity3102 were excluded from phase III trials of @entity15512 due to potential overlapping mechanism of action. The purpose of this study was to determine the clinical utility of @entity17931 and its impact on circulating @entity3800 following @entity3102 . EXPERIMENTAL DESIGN: Chemotherapy-na  ve @entity1 with progressive metastatic castration-resistant @entity263 (mCRPC) and prior @entity3102 therapy >= 28 days received @entity15512 1,000 mg daily and @entity229 5 mg twice daily. The primary endpoint was the proportion of @entity1 with @entity7735 response, defined as >= 30% @entity7735 decline at 12 weeks. H0 = 0.30 versus H1 = 0.50 (a = 0.05, power = 0.83). Circulating @entity342 levels were measured using liquid chromatography tandem mass spectrometry. RESULTS: Thirty-nine @entity1 were included in the final analysis. Twenty (51%; 95% confidence interval, 36%-66%) @entity1 had >= 30% @entity7735 decline; the null hypothesis was rejected. Sixteen (41%) had >= 50% @entity7735 decline. Median PFS (progression-free survival) was 16 weeks; median radiographic PFS (rPFS) was 36 weeks. Samples for measurement of baseline @entity3800 were available in 37 @entity1 . The @entity7735 response proportion was 59% in 29 @entity1 with @entity2494 >=  limit of quantitation (LOQ), compared with 13% in 8 @entity1 with @entity2494 < LOQ (P = 0.042). Median PFS was 6 and 16 weeks in @entity2494 < LOQ and @entity2494 >=  LOQ @entity1 , respectively (P = 0.017); median rPFS was 14 and 36 weeks in @entity2494 < LOQ and @entity2494 >=  LOQ @entity1 , respectively (P < 0.001). CONCLUSIONS: @entity17931 demonstrates modest clinical efficacy in mCRPC @entity1 previously treated with @entity3102 . @entity1 with @entity2494 >=  LOQ were more likely to demonstrate @entity7735 responses and longer PFS. Analysis of circulating @entity3800 merits further investigation as a biomarker for response to @entity342 synthesis inhibitor therapy. Clin @entity5 Res; 20(24); 6269-76.   2014 AACR.

Sequential use of the @entity342 synthesis inhibitors XXXX and @entity15512 in castration-resistant @entity263 and the predictive value of circulating @entity3800 .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity17931 :: ('MESH:C089740', 'Chemical') :: ['abiraterone', 'Abiraterone'] @entity7735 :: ('MESH:C563250', 'Disease') :: ['PSA'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer'] @entity15512 :: ('MESH:C089742', 'Chemical') :: ['abiraterone acetate'] @entity5 :: ('MESH:D009369', 'Disease') :: ['Cancer'] @entity3102 :: ('MESH:D007654', 'Chemical') :: ['ketoconazole'] @entity229 :: ('MESH:D011241', 'Chemical') :: ['prednisone'] @entity2494 :: ('MESH:D003687', 'Chemical') :: ['DHEA'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity3800 :: ('MESH:D000728', 'Chemical') :: ['androgens']
@entity3102 :: (MESH:D007654,Chemical) :: ['ketoconazole']
