{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:52:35Z","timestamp":1790232755675,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":3206,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Commonwealth Foundation for Cancer Research"},{"name":"David H. Koch Charitable Foundation"},{"name":"Conquer Cancer Foundation 2009 Young Investigator Award"},{"DOI":"10.13039\/100000005","name":"DOD","doi-asserted-by":"publisher","award":["W81XWH-09\u20131-0149"],"award-info":[{"award-number":["W81XWH-09\u20131-0149"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"DOD","doi-asserted-by":"publisher","award":["PC051385"],"award-info":[{"award-number":["PC051385"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30 CA006973"],"award-info":[{"award-number":["P30 CA006973"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["UL1 RR025005"],"award-info":[{"award-number":["UL1 RR025005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1RR025005"],"award-info":[{"award-number":["UL1RR025005"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH Roadmap for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background.<\/jats:title>\n                    <jats:p>The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling and delays tumor growth in murine prostate cancer xenograft models. We conducted a noncomparative, randomized, phase II study evaluating the antitumor efficacy of two doses of oral itraconazole in men with metastatic prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods.<\/jats:title>\n                    <jats:p>We randomly assigned 46 men with chemotherapy-na\u00efve metastatic castration-resistant prostate cancer (CRPC) to receive low-dose (200 mg\/day) or high-dose (600 mg\/day) itraconazole until disease progression or unacceptable toxicity. The primary endpoint was the prostate-specific antigen (PSA) progression-free survival (PPFS) rate at 24 weeks; a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints included the progression-free survival (PFS) rate and PSA response rate (Prostate Cancer Working Group criteria). Exploratory outcomes included circulating tumor cell (CTC) enumeration, serum androgen measurements, as well as pharmacokinetic and pharmacodynamic analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results.<\/jats:title>\n                    <jats:p>The high-dose arm enrolled to completion (n = 29), but the low-dose arm closed early (n = 17) because of a prespecified futility rule. The PPFS rates at 24 weeks were 11.8% in the low-dose arm and 48.0% in the high-dose arm. The median PFS times were 11.9 weeks and 35.9 weeks, respectively. PSA response rates were 0% and 14.3%, respectively. In addition, itraconazole had favorable effects on CTC counts, and it suppressed Hedgehog signaling in skin biopsy samples. Itraconazole did not reduce serum testosterone or dehydroepiandrostenedione sulfate levels. Common toxicities included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia, hypertension, and edema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion.<\/jats:title>\n                    <jats:p>High-dose itraconazole (600 mg\/day) has modest antitumor activity in men with metastatic CRPC that is not mediated by testosterone suppression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2012-314","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T02:26:35Z","timestamp":1358907995000},"page":"163-173","source":"Crossref","is-referenced-by-count":158,"title":["Repurposing Itraconazole as a Treatment for Advanced Prostate Cancer: A Noncomparative Randomized Phase II Trial in Men With Metastatic Castration-Resistant Prostate Cancer"],"prefix":"10.1093","volume":"18","author":[{"given":"Emmanuel S.","family":"Antonarakis","sequence":"first","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth I.","family":"Heath","sequence":"additional","affiliation":[{"name":"b Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Smith","sequence":"additional","affiliation":[{"name":"c University of Michigan, Ann Arbor, Michigan, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Rathkopf","sequence":"additional","affiliation":[{"name":"d Memorial Sloan-Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Blackford","sequence":"additional","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Danila","sequence":"additional","affiliation":[{"name":"d Memorial Sloan-Kettering Cancer Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serina","family":"King","sequence":"additional","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Frost","sequence":"additional","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Seun","family":"Ajiboye","sequence":"additional","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhao","sequence":"additional","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Mendonca","sequence":"additional","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushant K.","family":"Kachhap","sequence":"additional","affiliation":[{"name":"a Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Rudek","sequence":"additional","affiliation":[{"name":"a Sidney 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