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Although the precise pathogenesis and mechanisms of HFS remain unclear, inflammatory reactions are thought to be involved. The preventive effects of topical diclofenac gel have been reported from India. However, the trial did not evaluate its preventive effect for the sole, and the HFS incidence in the control group was lower than that in previous reports. Therefore, this study aims to confirm the preventive effects of diclofenac sodium 0.1% cream for capecitabine-induced HFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. Patients scheduled to receive capecitabine-containing chemotherapy are enrolled, and participants are prophylactically treated with topical diclofenac sodium 0.1% cream or placebo alongside standard preventive therapy. The primary endpoint is an incidence of grade 2 HFS within 3\u00a0months. The secondary endpoints include time to onset of HFS, incidences of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, dose intensity of capecitabine, an incidence of grade\u2009\u2265\u20092 peripheral sensory neuropathy, incidences of other capecitabine-related adverse events (nausea, vomiting, appetite loss, diarrhea, oral mucositis, pigmentation, abnormality of liver and renal functions, and neutropenia).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>If this study meets the primary endpoint, a new standard preventive therapy for HFS will be established. Moreover, the use of topical diclofenac cream alongside high-dose capecitabine may enhance chemotherapy efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-025-02789-z","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T16:20:46Z","timestamp":1747239646000},"page":"1553-1561","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A randomized, double-blind, placebo-controlled phase III study evaluating the preventive effect of diclofenac cream on capecitabine-related hand-foot syndrome: study protocol of J-SUPPORT2401\/JORTC-SUP06 (J-DIRECT)"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3473-8244","authenticated-orcid":false,"given":"Yohei","family":"Iimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ishiguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Nojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Oyamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Ariyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Hirakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadamoto","family":"Zenda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narikazu","family":"Boku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"2789_CR1","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1634\/theoncologist.2011-0033","volume":"16","author":"V Sibaud","year":"2011","unstructured":"Sibaud V, Dalenc F, Chevreau C et al (2011) HFS-14, a specific quality of life scale developed for patients suffering from hand-foot syndrome. 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This clinical trial was conducted in compliance with the Clinical Trials Act in Japan and was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031240705.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients were required to provide written informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Personal information, such as name, address, and medical ID, will be not collected.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Confidentiality"}},{"value":"The study will be initiated in April 2025. We expect to complete the recruitment by March 2027.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Trial status"}}]}}