{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:42:16Z","timestamp":1775673736103,"version":"3.50.1"},"reference-count":11,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K09315"],"award-info":[{"award-number":["23K09315"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K09315"],"award-info":[{"award-number":["23K09315"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral mucositis is a frequent adverse effect of chemotherapy that significantly affects patients\u2019 quality of life and treatment continuity. Despite its clinical relevance, effective preventive strategies remain limited. This study aims to compare the efficacy and safety of betamethasone mouthwash with those of sodium gualenate hydrate mouthwash for preventing chemotherapy-induced oral mucositis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This Phase II, multicenter, open-label, randomized controlled trial aims to enroll 296 adult patients (\u226518 years) undergoing chemotherapy for solid tumors (excluding head and neck and hematological cancers). Participants will be randomized 1:1 into two arms: a betamethasone mouthwash (intervention) group and a sodium gualenate hydrate mouthwash (control) group. The primary outcome is the prevention of Grade 1 oral mucositis, assessed using the Common Terminology Criteria for Adverse Events v3.0 and v5.0. Secondary outcomes include prevention of Grade 2\u20133 oral mucositis, the incidence of oral candidiasis, and chemotherapy completion rates. Data will be analyzed using Kaplan\u2013Meier survival curves, log-rank tests, and Cox regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Expected Outcomes<\/jats:title>\n                    <jats:p>This study aims to establish betamethasone mouthwash as an effective preventive strategy for potentially enhancing the quality of life of patients with cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>This study was registered with the Japan Registry of Clinical Trials on September 20, 2024 (jRCTs071240060).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0345991","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T17:29:06Z","timestamp":1775669346000},"page":"e0345991","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevention of oral mucositis in patients undergoing cancer chemotherapy using betamethasone mouthwash: A multicenter randomized controlled trial protocol"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4646-587X","authenticated-orcid":true,"given":"Sakiko","family":"Soutome","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomofumi","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-8062","authenticated-orcid":true,"given":"Eiji","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Nakahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0409-6252","authenticated-orcid":true,"given":"Tatsushi","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaya","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Tomihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Ueki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Noda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Shimanishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madoka","family":"Funahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Kawahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiko","family":"Yamamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinpei","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensuke","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanshiro","family":"Kanazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minako","family":"Otsuji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagato","family":"Natsume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Umeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Research Committee of the Japanese Society of Oral Care","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"issue":"1","key":"pone.0345991.ref001","first-page":"21","article-title":"A biological approach to mucositis","volume":"2","author":"ST Sonis","year":"2004","journal-title":"J Support Oncol"},{"issue":"1","key":"pone.0345991.ref002","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13046-020-01715-7","article-title":"Oral mucositis: the hidden side of cancer therapy","volume":"39","author":"C Pulito","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"issue":"10","key":"pone.0345991.ref003","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1002\/cncr.28592","article-title":"MASCC\/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","volume":"120","author":"RV Lalla","year":"2014","journal-title":"Cancer"},{"issue":"1","key":"pone.0345991.ref004","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-056781","article-title":"Preventive effects of betamethasone valerate ointment for radiation-induced severe oral mucositis in patients with oral or oropharyngeal cancer: protocol for a multicentre, phase II, randomised controlled trial (Bet-ROM study)","volume":"12","author":"S Soutome","year":"2022","journal-title":"BMJ Open"},{"issue":"5","key":"pone.0345991.ref005","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/S1470-2045(17)30109-2","article-title":"Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial","volume":"18","author":"HS Rugo","year":"2017","journal-title":"Lancet Oncol"},{"issue":"2","key":"pone.0345991.ref006","doi-asserted-by":"crossref","DOI":"10.1634\/theoncologist.2019-0382","article-title":"Oral Care Evaluation to Prevent Oral Mucositis in Estrogen Receptor-Positive Metastatic Breast Cancer Patients Treated with Everolimus (Oral Care-BC): A Randomized Controlled Phase III Trial","volume":"25","author":"N Niikura","year":"2020","journal-title":"Oncologist"},{"issue":"7","key":"pone.0345991.ref007","doi-asserted-by":"crossref","first-page":"535","DOI":"10.21037\/atm-20-6488","article-title":"Oral care and oral assessment guide in breast cancer patients receiving everolimus and exemestane: subanalysis of a randomized controlled trial (Oral Care-BC)","volume":"9","author":"M Umeda","year":"2021","journal-title":"Ann Transl Med"},{"issue":"5","key":"pone.0345991.ref008","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.5794\/jjoms.26.1399","article-title":"A double-blind study on clinical effects of Dexaltin ointment","volume":"26","author":"T UENO","year":"1980","journal-title":"Jpn J Oral Maxillofac Surg"},{"issue":"3","key":"pone.0345991.ref009","first-page":"1069","article-title":"Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas: a retrospective multicenter study of 326 patients","volume":"28","author":"M Nishii","year":"2020","journal-title":"Support Care Cancer"},{"issue":"9","key":"pone.0345991.ref010","article-title":"Efficacy and Safety of Topical Steroid Therapy for Oral Mucositis During Cancer Chemotherapy: A Scoping Review","volume":"17","author":"M Funahara","year":"2025","journal-title":"Cureus"},{"issue":"3","key":"pone.0345991.ref011","doi-asserted-by":"crossref","first-page":"101896","DOI":"10.1016\/j.jebdp.2023.101896","article-title":"Efficacy and safety of a dexamethasone-based mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study","volume":"23","author":"S Kuba","year":"2023","journal-title":"J Evid Based Dent Pract"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0345991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T17:29:08Z","timestamp":1775669348000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0345991"}},"subtitle":[],"editor":[{"given":"Maria Giulia","family":"Nosotti","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":11,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0345991","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]}}}