{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:04:24Z","timestamp":1791921864653,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Consensus guidelines exist for genotype\u2010guided fluoropyrimidine dosing based on variation in the gene dihydropyrimidine dehydrogenase (<jats:italic>DPYD<\/jats:italic>). However, these guidelines have not been widely implemented in North America and most studies of pretreatment <jats:italic>DPYD<\/jats:italic> screening have been conducted in Europe. Given regional differences in treatment practices and rates of adverse events (AEs), we investigated the impact of pretreatment <jats:italic>DPYD<\/jats:italic> genotyping on AEs in a Canadian context. Patients referred for <jats:italic>DPYD<\/jats:italic> genotyping prior to fluoropyrimidine treatment were enrolled from December 2013 through November 2019 and followed until completion of fluoropyrimidine treatment. Patients were genotyped for <jats:italic>DPYD<\/jats:italic> c.1905+1G&gt;A, c.2846A&gt;T, c.1679T&gt;G, and c.1236G&gt;A. Genotype\u2010guided dosing recommendations were informed by Clinical Pharmacogenetics Implementation Consortium guidelines. The primary outcome was the proportion of patients who experienced a severe fluoropyrimidine\u2010related AE (grade \u22653, Common Terminology Criteria for Adverse Events version 5.0). Secondary outcomes included early severe AEs, severe AEs by toxicity category, discontinuation of fluoropyrimidine treatment due to AEs, and fluoropyrimidine\u2010related death. Among 1394 patients, mean (SD) age was 64 (12) years, 764 (54.8%) were men, and 47 (3.4%) were <jats:italic>DPYD<\/jats:italic> variant carriers treated with dose reduction. Eleven variant carriers (23%) and 418 (31.0%) noncarriers experienced a severe fluoropyrimidine\u2010related AE (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.265). Six carriers (15%) and 284 noncarriers (21.1%) experienced early severe fluoropyrimidine\u2010related AEs (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.167). <jats:italic>DPYD<\/jats:italic> variant carriers treated with genotype\u2010guided dosing did not experience an increased risk for severe AEs. Our data support a role for <jats:italic>DPYD<\/jats:italic> genotyping in the use of fluoropyrimidines in North America.<\/jats:p>","DOI":"10.1111\/cts.12981","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T12:17:16Z","timestamp":1614082636000},"page":"1338-1348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Impact of pretreatment dihydropyrimidine dehydrogenase genotype\u2010guided fluoropyrimidine dosing on chemotherapy associated adverse events"],"prefix":"10.1111","volume":"14","author":[{"given":"Theodore J.","family":"Wigle","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandi L.","family":"Povitz","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Medwid","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Western Ontario London Canada"},{"name":"Department of Medicine University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Teft","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin M.","family":"Legan","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lenehan","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Nevison","sequence":"additional","affiliation":[{"name":"School of Medicine University of Toronto Mississauga Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veera","family":"Panuganty","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Keller","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymie","family":"Mailloux","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Western Ontario London Canada"},{"name":"Department of Medicine University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Siebring","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisira","family":"Sarma","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Welch","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Winquist","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute I.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology University of Western Ontario London Canada"},{"name":"Department of Medicine University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Hoffman\u2010La Roche Ltd.Xeloda (Capecitabine) Product Monograph. 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