{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:15:56Z","timestamp":1790612156253,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T00:00:00Z","timestamp":1544572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010795","name":"Chugai Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009954","name":"Taiho Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007054","name":"Meso Scale Diagnostics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002973","name":"Daiichi-Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002973","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,2]]},"abstract":"Studies have indicated an association between UDP<\/jats:styled-content>\u2010glucuronosyltransferase\u20101A1 (UGT<\/jats:styled-content>1A1<\/jats:italic>) genetic polymorphisms and irinotecan\u2010induced toxicity. We undertook this study to investigate the association between UGT<\/jats:styled-content>1A1<\/jats:italic> genetic polymorphisms and toxicity in patients treated with the FOLFIRINOX<\/jats:styled-content> (comprising oxaliplatin, irinotecan, fluorouracil, and leucovorin) chemotherapy regimen in the JASPAC<\/jats:styled-content> 06 study. Patients screened for UGT<\/jats:styled-content>1A1*6 and UGT<\/jats:styled-content>1A1*28, and treated with either the original FOLFIRINOX<\/jats:styled-content> (oxaliplatin 85\u00a0mg\/m2<\/jats:sup>, irinotecan 180\u00a0mg\/m2<\/jats:sup>, leucovorin 200\u00a0mg\/m2<\/jats:sup>, bolus 5\u2010fluorouracil [5\u2010FU<\/jats:styled-content>] 400\u00a0mg\/m2<\/jats:sup>, and continuous 5\u2010FU<\/jats:styled-content> 2400\u00a0mg\/m2<\/jats:sup>) or a modified FOLFIRINOX<\/jats:styled-content> (oxaliplatin 85\u00a0mg\/m2<\/jats:sup>, irinotecan 150\u00a0mg\/m2<\/jats:sup>, leucovorin 200\u00a0mg\/m2<\/jats:sup>, and continuous 5\u2010FU<\/jats:styled-content> 2400\u00a0mg\/m2<\/jats:sup>) as first\u2010line chemotherapy were included. Of 199 patients eligible for this analysis, 79 patients were treated with the original FOLFIRINOX<\/jats:styled-content> regimen and 120 patients were treated with the modified FOLFIRINOX<\/jats:styled-content> regimen. In the original FOLFIRINOX<\/jats:styled-content> group, 54 were UGT<\/jats:styled-content>1A1<\/jats:italic> WT, and 25 were UGT<\/jats:styled-content>1A1<\/jats:italic> heterozygous type (\u2212\/*6, 12 patients; \u2212\/*28, 13 patients). In the modified FOLFIRINOX<\/jats:styled-content> group, 64 were UGT<\/jats:styled-content>1A1<\/jats:italic> WT and 56 were UGT<\/jats:styled-content>1A1<\/jats:italic> heterozygous type (\u2212\/*6, 33 patients; \u2212\/*28, 23 patients).<\/jats:p>In the original FOLFIRINOX<\/jats:styled-content> group, the incidence of diarrhea was significantly higher among patients with UGT<\/jats:styled-content>1A1<\/jats:italic> heterozygous type than among those with UGT<\/jats:styled-content>1A1<\/jats:italic> WT and the incidence of leukopenia and diarrhea was significantly higher among patients with UGT<\/jats:styled-content>1A1<\/jats:italic> \u2212\/*6 than among those with UGT<\/jats:styled-content>1A1<\/jats:italic> \u2212\/*28. Patients with UGT<\/jats:styled-content>1A1<\/jats:italic> heterozygous type, especially those with UGT<\/jats:styled-content>1A1<\/jats:italic> \u2212\/*6, tended to show a higher incidence rate of severe adverse events, but this was not statistically significant. However, for patients who received the modified FOLFIRINOX<\/jats:styled-content>, there was no difference in the frequency of adverse events due to UGT<\/jats:styled-content>1A1<\/jats:italic> status. In conclusion, patients with heterozygous UGT<\/jats:styled-content>1A1<\/jats:italic> polymorphisms treated with the original FOLFIRINOX<\/jats:styled-content> regimen experienced severe toxicity more frequently than patients with WT UGT<\/jats:styled-content>1A1<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/cas.13883","type":"journal-article","created":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T12:49:27Z","timestamp":1542458967000},"page":"707-716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Impact of UGT<\/scp>1A1<\/i> genetic polymorphism on toxicity in unresectable pancreatic cancer patients undergoing FOLFIRINOX<\/scp>"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7952-5528","authenticated-orcid":false,"given":"Hiromichi","family":"Shirasu","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Oncology Shizuoka Cancer Center Shizuoka 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