{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:38:56Z","timestamp":1771519136218,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K07204"],"award-info":[{"award-number":["19K07204"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regorafenib improves the survival of patients with metastatic colorectal cancer (mCRC); however, it is also characterized by detrimental dermal side effects that may require treatment cessation or modified dosing. In our previous prospective pharmacokinetic, pharmacodynamic, and pharmacogenetic studies, 17.5% (7\/40) of the patients with mCRC had grade 3 erythema multiforme (EM) that caused treatment discontinuation. Haplotypes in genes encoding human leukocyte antigen (HLA) are associated with EM following the administration of drugs, such as allopurinol. This study examined the association between <jats:italic>HLA<\/jats:italic> haplotypes and regorafenib\u2010induced EM. Regorafenib was administered orally at 160\u2009mg\/body once daily for weeks 1\u20133 of each 4\u2010week\u2009cycle. To determine the <jats:italic>HLA<\/jats:italic> haplotypes, we used the WAKFlow HLA Typing Kit HLA\u2010A, \u2010B, or \u2010C. The carrier frequency of <jats:italic>HLA\u2010C*01:02<\/jats:italic> in patients with EM (6\/7) was higher than that in tolerant controls (8\/33; odds ratio [OR]\u2009=\u200918.8, 95% confidence interval [CI]\u2009=\u20091.95\u2013180, <jats:italic>p<\/jats:italic>\u2009=\u20090.00437). <jats:italic>HLA\u2010B*46:01<\/jats:italic> was also associated with EM (OR\u2009=\u200911.6, 95% CI\u2009=\u20091.47\u201392.1, <jats:italic>p<\/jats:italic>\u2009=\u20090.0299). These associations were no longer significant after Bonferroni correction for multiple testing. Therefore, regorafenib\u2010induced EM in Japanese patients appears to be associated with specific <jats:italic>HLA<\/jats:italic> haplotypes but further validation is needed.<\/jats:p>","DOI":"10.1111\/cts.13589","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T07:56:15Z","timestamp":1688975775000},"page":"1741-1747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Associations of <i>HLA\u2010C*01:02<\/i> and <i>HLA\u2010B*46:01<\/i> with regorafenib\u2010induced erythema multiforme in Japanese patients with metastatic colorectal cancer"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1575-6690","authenticated-orcid":false,"given":"Ken\u2010ichi","family":"Fujita","sequence":"first","affiliation":[{"name":"Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy Showa University School of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsumi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy Showa University School of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remi","family":"Murase","sequence":"additional","affiliation":[{"name":"Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy Showa University School of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Takeshima","sequence":"additional","affiliation":[{"name":"Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy Showa University School of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroo","family":"Ishida","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Showa University Northern Yokohama Hospital  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaro","family":"Kubota","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine Showa University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.10.011"},{"key":"e_1_2_10_3_1","unstructured":"US Food and Drug Administration (FDA).Clinical pharmacology and biopharmaceutics review(s).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2012\/203085Orig1s000ClinPharmR.pdf. 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