{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:21:32Z","timestamp":1774084892345,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012030","name":"Yakult Honsha","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Effective second\u2010line chemotherapy options are limited in treating advanced biliary tract cancers (BTCs). Resminostat is an oral histone deacetylase inhibitor. Such inhibitors increase sensitivity to fluorouracil, the active form of S\u20101. In the phase I study, addition of resminostat to S\u20101 was suggested to have promising efficacy for pre\u2010treated BTCs. This study investigated the efficacy and safety of resminostat plus S\u20101 in second\u2010line therapy for BTCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were randomly assigned to receive resminostat or placebo (200\u00a0mg orally per day; days 1\u20135 and 8\u201312) and S\u20101 group (80\u2013120\u00a0mg orally per day by body surface area; days 1\u201314) over a 21\u2010day cycle. The primary endpoint was progression\u2010free survival (PFS). Secondary endpoints comprised overall survival (OS), response rate (RR), disease control rate (DCR), and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 101 patients enrolled, 50 received resminostat+S\u20101 and 51 received placebo+S\u20101. Median PFS was 2.9\u00a0months for resminostat+S\u20101 vs. 3.0\u00a0months for placebo+S\u20101 (HR: 1.154, 95% CI: 0.759\u20131.757, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.502); median OS was 7.8\u00a0months vs. 7.5\u00a0months, respectively (HR: 1.049, 95% CI: 0.653\u20131.684, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.834); the RR and DCR were 6.0% vs. 9.8% and 70.0% vs. 78.4%, respectively. Treatment\u2010related adverse events (TrAEs) of grade\u00a0\u2265\u00a03 occurring more frequently (\u226510% difference) in the resminostat+S\u20101 than in the placebo+S\u20101 comprised platelet count decreased (18.0% vs. 2.0%) and decreased appetite (16.0% vs. 2.0%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Resminostat plus S\u20101 therapy improved neither PFS nor OS for patients with pre\u2010treated BTCs. Addition of resminostat to S\u20101 was associated with higher incidence of TrAEs, but these were manageable (JapicCTI\u2010183883).<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3813","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T14:56:27Z","timestamp":1614351387000},"page":"2088-2099","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A randomized, double\u2010blind, phase II study of oral histone deacetylase inhibitor resminostat plus S\u20101 versus placebo plus S\u20101 in biliary tract cancers previously treated with gemcitabine plus platinum\u2010based chemotherapy"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-0029","authenticated-orcid":false,"given":"Makoto","family":"Ueno","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division Kanagawa Cancer Center 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousuke","family":"Nakai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Department of Endoscopy and Endoscopic Surgery Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Oncology Hyogo Cancer Center Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Ozaka","sequence":"additional","affiliation":[{"name":"Hepato\u2010Biliary\u2010Pancreatic Medicine Department Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobumasa","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Aichi Cancer Center Hospital Aichi 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Katanuma","sequence":"additional","affiliation":[{"name":"Center for Gastroenterology Teine\u2010keijinkai hospital Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshikazu","family":"Moriwaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kajiwara","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology National Hospital Organization Shikoku Cancer Center Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ishii","sequence":"additional","affiliation":[{"name":"Clinical Research Center Chiba Cancer Center Chiba 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