{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:04:09Z","timestamp":1792883049077,"version":"4.5.0"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Studies indicate that castration-resistant prostate cancer (CRPC) remains driven by ligand-dependent androgen receptor (AR) signaling. To evaluate this, a trial of abiraterone acetate\u2014a potent, selective, small-molecule inhibitor of cytochrome P (CYP) 17, a key enzyme in androgen synthesis\u2014was pursued.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Chemotherapy-na\u00efve men (n = 21) who had prostate cancer that was resistant to multiple hormonal therapies were treated in this phase I study of once-daily, continuous abiraterone acetate, which escalated through five doses (250 to 2,000 mg) in three-patient cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Abiraterone acetate was well tolerated. The anticipated toxicities attributable to a syndrome of secondary mineralocorticoid excess\u2014namely hypertension, hypokalemia, and lower-limb edema\u2014were successfully managed with a mineralocorticoid receptor antagonist. Antitumor activity was observed at all doses; however, because of a plateau in pharmacodynamic effect, 1,000 mg was selected for cohort expansion (n = 9). Abiraterone acetate administration was associated with increased levels of adrenocorticotropic hormone and steroids upstream of CYP17 and with suppression of serum testosterone, downstream androgenic steroids, and estradiol in all patients. Declines in prostate-specific antigen \u2265 30%, 50%, and 90% were observed in 14 (66%), 12 (57%), and 6 (29%) patients, respectively, and lasted between 69 to \u2265 578 days. Radiologic regression, normalization of lactate dehydrogenase, and improved symptoms with a reduction in analgesic use were documented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC. These data confirm that CRPC commonly remains dependent on ligand-activated AR signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2007.15.9749","type":"journal-article","created":{"date-parts":[[2008,7,21]],"date-time":"2008-07-21T20:58:50Z","timestamp":1216673930000},"page":"4563-4571","source":"Crossref","is-referenced-by-count":766,"title":["Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven"],"prefix":"10.1200","volume":"26","author":[{"given":"Gerhardt","family":"Attard","sequence":"first","affiliation":[{"name":"From the Royal Marsden NHS Foundation Trust; and The Institute of Cancer Research, Sutton, Surrey, United Kingdom; and Cougar Biotechnology, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison H.M.","family":"Reid","sequence":"additional","affiliation":[{"name":"From the Royal Marsden NHS Foundation Trust; 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