{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:51:52Z","timestamp":1788303112068,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007117","name":"Peter Michael Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007117","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co\u2010administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen\u2010receptor signaling. However, prior trials of DSF in PC used DSF as monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the safety and efficacy of concurrent administration of DSF with Cu, we conducted a phase 1b clinical trial of patients with metastatic castration\u2010resistant prostate cancer (mCRPC) receiving Cu with DSF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, setting, and participants<\/jats:title><jats:p>Patients with mCRPC were treated in two cohorts: mCRPC with nonliver\/peritoneal metastases (A), and mCRPC with liver and\/or peritoneal metastases (B). Baseline Cu avidity was measured by <jats:sup>64<\/jats:sup>CuCl<jats:sub>2<\/jats:sub> PET scan. Intravenous (IV) CuCl<jats:sub>2<\/jats:sub> was given weekly for three doses with oral daily DSF followed by daily oral Cu gluconate and DSF until disease progression. DSF and metabolite diethyldithiocarbamic acid methyl ester (Me\u2010DDC) levels in plasma were measured. DSF and Me\u2010DDC were then assessed for cytotoxicity in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We treated nine patients with mCRPC (six on cohort A and three on cohort B). Bone and nodal metastases showed differential and heterogeneous Cu uptake on <jats:sup>64<\/jats:sup>CuCl<jats:sub>2<\/jats:sub> PET scans. No confirmed PSA declines or radiographic responses were observed. Median PFS was 2.8\u2009months and median OS was 8.3\u2009months. Common adverse events included fatigue and psychomotor depression; no Grade 4\/5 AEs were observed. Me\u2010DDC was measurable in all samples (LOQ\u2009=\u20090.512\u2009ng\/ml), whereas DSF was not (LOQ\u2009=\u20090.032\u2009ng\/ml, LOD\u2009=\u20090.01\u2009ng\/ml); Me\u2010DDC was not cytotoxic in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Oral DSF is not an effective treatment for mCRPC due to rapid metabolism into an inactive metabolite, Me\u2010DDC. This trial has stopped enrollment and further work is needed to identify a stable DSF formulation for treatment of mCRPC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24329","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T17:42:26Z","timestamp":1647279746000},"page":"858-866","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Prospective clinical trial of disulfiram plus copper in men with metastatic castration\u2010resistant prostate cancer"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-3531","authenticated-orcid":false,"given":"Tian","family":"Zhang","sequence":"first","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers Duke University Durham North Carolina USA"},{"name":"Division of Medical Oncology, Department of Medicine Duke University Durham North Carolina USA"},{"name":"Division of Hematology 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Daly","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Spasojevic","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subha","family":"Bakthavatsalam","sequence":"additional","affiliation":[{"name":"Department of Chemistry Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Franz","sequence":"additional","affiliation":[{"name":"Department of Chemistry Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Berg","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia S.","family":"Karachaliou","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga G.","family":"James","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Radiology Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Halabi","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers Duke University Durham North Carolina USA"},{"name":"Division of Medical Oncology, Department of Medicine Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Center for Prostate and Urologic Cancers Duke University Durham North Carolina USA"},{"name":"Division of Medical Oncology, Department of Medicine Duke University Durham North Carolina USA"},{"name":"Division of Urology, Department of Surgery 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