Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY; University of Twente, Department of Medical Cell BioPhysics, Enschede, the Netherlands; and Cougar Biotechnology, Los Angeles; and Department of Medicine, University of California, San Francisco, CA.
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).
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.
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.
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.
Written by:
Reid AH, Attard G, Danila DC, Oommen NB, Olmos D, Fong PC, Molife LR, Hunt J, Messiou C, Parker C, Dearnaley D, Swennenhuis JF, Terstappen LW, Lee G, Kheoh T, Molina A, Ryan CJ, Small E, Scher HI, de Bono JS. Are you the author?
Reference:
J Clin Oncol. 2010 Feb 16. Epub ahead of print.
doi:10.1200/JCO.2009.24.6819
PubMed Abstract
PMID:20159823
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