{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T09:31:44Z","timestamp":1772184704901,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T00:00:00Z","timestamp":1445558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NCI\/CTEP Phase 2 Consortium","award":["N01-CM-2011-00071C"],"award-info":[{"award-number":["N01-CM-2011-00071C"]}]},{"name":"Department of Defense Prostate Cancer Research Program Idea Award","award":["W81XWH-11-1-0422"],"award-info":[{"award-number":["W81XWH-11-1-0422"]}]},{"name":"Prostate Cancer Foundation Young Investigator Award"},{"name":"St. Anthony Prostate Cancer Research Fund"},{"name":"CD McKinnon Memorial Neuroendocrine Prostate Cancer Fund"},{"name":"Berns Family Prostate Cancer Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Fyn is a kinase that is upregulated in a subset of metastatic castration\u2010resistant prostate cancer. Saracatinib potently inhibits Fyn activation. We have noted a relationship between Fyn expression and directional motility, a cellular process related to metastasis. As such we hypothesized that treatment with saracatinib would increase the time required to develop new metastatic lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Patients with metastatic castration\u2010resistant prostate cancer that had progressed after docetaxel were eligible for enrollment. This study was executed as a randomized discontinuation trial. During a lead\u2010in phase of two 28\u2010Day cycles, all patients received saracatinib. Afterward, patients with radiographically stable disease were randomized to either saracatinib or placebo. Patients continued treatment until evidence of new metastasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Thirty\u2010one patients were treated. Only 26% of patients had stable disease after 8 weeks and thus proceeded to randomization. This required early termination of the study for futility. The 70% of patients who progressed after the lead\u2010in phase exhibited expansion of existing lesions or decompensation due to clinical progression without new metastatic lesions. Fatigue was reported in more than 25% of patients (all grades) with only two patients experiencing grade 3 toxicity. Other grade 3 adverse events included dehydration, thrombocytopenia, and weakness.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>This study was unable to determine if saracatinib had potential as metastasis inhibitor. Metastasis inhibition by saracatinib may still be viable in an earlier time in the disease history. <jats:italic>Prostate 76:286\u2013293, 2016<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23119","type":"journal-article","created":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T21:20:05Z","timestamp":1445635205000},"page":"286-293","source":"Crossref","is-referenced-by-count":30,"title":["Saracatinib as a metastasis inhibitor in metastatic castration\u2010resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD\/PCF Prostate Cancer Clinical Trials Consortium Study"],"prefix":"10.1002","volume":"76","author":[{"given":"Edwin M.","family":"Posadas","sequence":"first","affiliation":[{"name":"Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars\u2010Sinai Medical Center, Los Angeles California"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Cedars\u2010Sinai Medical Center, Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafi S.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars\u2010Sinai Medical Center, Los Angeles California"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Cedars\u2010Sinai Medical Center, Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore","family":"Karrison","sequence":"additional","affiliation":[{"name":"Biostatistics, Department of Health Service, University of Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell Z.","family":"Szmulewitz","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Program, Section of Hematology\/Oncology, Department of Medicine, University of Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Program, Section of Hematology\/Oncology, Department of Medicine, University of Chicago, Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"James L.","family":"Wade","sequence":"additional","affiliation":[{"name":"Cancer Care Specialists of Central Illinois, S.C, Decatur Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Shen","sequence":"additional","affiliation":[{"name":"Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars\u2010Sinai Medical Center, Los Angeles California"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Cedars\u2010Sinai Medical Center, Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murali","family":"Gururajan","sequence":"additional","affiliation":[{"name":"Urologic Oncology Program, Samuel Oschin 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