Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate Journal Article

   

Authors:	Reid, A. H. M.; Attard, G.; Danila, D. C.; Oommen, N. B.; Olmos, D.; Fong, P. C.; Molife, L. R.; Hunt, J.; Messiou, C.; Parker, C.; Dearnaley, D.; Swennenhuis, J. F.; Terstappen, Lwmm; Lee, G.; Kheoh, T.; Molina, A.; Ryan, C. J.; Small, E.; Scher, H. I.; de Bono, J. S.
Article Title:	Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate
Abstract:	Purpose The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). Patients and Methods In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of >= 50% in at least seven of 35 patients. Per an attained phase II design, more than 35 patients could be enrolled if the primary end point was met. Secondary objectives included: PSA declines of >= 30% and >= 90%; rate of RECIST (Response Evaluation Criteria in Solid Tumors) responses and duration on study; time to PSA progression; safety and tolerability; and circulating tumor cell (CTC) enumeration. Results Docetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of >= 30%, >= 50% and >= 90% were seen in 68% (32 of 47), 51% (24 of 47), and 15% (seven of 47) of patients, respectively. Partial responses (by RECIST) were reported in eight (27%) of 30 patients with measurable disease. Median time to PSA progression was 169 days (95% CI, 113 to 281 days). The median number of weeks on study was 24, and 12 (25.5%) of 47 patients remained on study >= 48 weeks. CTCs were enumerated in 34 patients; 27 (79%) of 34 patients had at least five CTCs at baseline. Eleven (41%) of 27 patients had a decline from at least five to less than 5 CTCs, and 18 (67%) of 27 had a >= 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated. Conclusion Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent.
Keywords:	survival; drug development; end-points; testosterone; androgens; recommendations; expression; group; working; circulating tumor-cells; ii clinical-trials
Journal Title:	Journal of Clinical Oncology
Volume:	28
Issue:	9
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2010-03-20
Start Page:	1489
End Page:	1495
Language:	English
ACCESSION:	ISI:000275824600009
DOI:	10.1200/jco.2009.24.6819
PROVIDER:	wos
PMCID:	PMC2849770
PUBMED:	20159823
Notes:	--- - Article - "Source: Wos"

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