{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:47:14Z","timestamp":1787611634268,"version":"build-2736575974"},"reference-count":18,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2010,3,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs), extragonadal androgen sources may sustain tumor growth despite a castrate environment. This phase I dose-escalation study of abiraterone acetate evaluated safety, pharmacokinetics, and effects on steroidogenesis and prostate-specific antigen (PSA) levels in men with CPRC with or without prior ketoconazole therapy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Thirty-three men with chemotherapy-na\u00efve progressive CRPC were enrolled. Nineteen patients (58%) had previously received ketoconazole for CRPC. Bone metastases were present in 70% of patients, and visceral involvement was present in 18%. Three patients (9%) had locally advanced disease without distant metastases. Fasted or fed cohorts received abiraterone acetate doses of 250, 500, 750, or 1,000 mg daily. Single-dose pharmacokinetic analyses were performed before continuous daily dosing. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Adverse events were predominantly grade 1 or 2. No dose-limiting toxicities were observed. Hypertension (grade 3, 12%) and hypokalemia (grade 3, 6%; grade 4, 3%) were the most frequent serious toxicities and responded to medical management. Confirmed \u2265 50% PSA declines at week 12 were seen in 18 (55%) of 33 patients, including nine (47%) of 19 patients with prior ketoconazole therapy and nine (64%) of 14 patients without prior ketoconazole therapy. Substantial declines in circulating androgens and increases in mineralocorticoids were seen with all doses. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Abiraterone acetate was well tolerated and demonstrated activity in CRPC, including in patients previously treated with ketoconazole. Continued clinical study is warranted. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2009.24.1281","type":"journal-article","created":{"date-parts":[[2010,2,17]],"date-time":"2010-02-17T05:10:00Z","timestamp":1266383400000},"page":"1481-1488","source":"Crossref","is-referenced-by-count":338,"title":["Phase I Clinical Trial of the CYP17 Inhibitor Abiraterone Acetate Demonstrating Clinical Activity in Patients With Castration-Resistant Prostate Cancer Who Received Prior Ketoconazole Therapy"],"prefix":"10.1200","volume":"28","author":[{"given":"Charles J.","family":"Ryan","sequence":"first","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Smith","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Fong","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Kantoff","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Raynaud","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Martins","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thian","family":"Kheoh","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Molina","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Small","sequence":"additional","affiliation":[{"name":"From the Urologic Oncology Program, University of California, San Francisco; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco; Cougar Biotechnology, Los Angeles, CA; Massachusetts General Hospital; Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA; and Institute of Cancer Research, Drug Metabolism and Pharmacokinetics Team, Belmont, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040720"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.4008"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041318"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ncpuro0435"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0067"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63112-4"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp048178"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.4777"},{"key":"B9","first-page":"3550","volume":"61","author":"Linja MJ","year":"2001","journal-title":"Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4000"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.06.037"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(03)00070-0"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.9749"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.11.3461"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(88)90295-6"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2006.06.071"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2344"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2009.24.1281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T22:48:57Z","timestamp":1653518937000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2009.24.1281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,20]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2010,3,20]]}},"alternative-id":["10.1200\/JCO.2009.24.1281"],"URL":"https:\/\/doi.org\/10.1200\/jco.2009.24.1281","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,20]]}}}