{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:21:23Z","timestamp":1787862083620,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:p>Patients carrying <jats:italic>DPYD<\/jats:italic> variant alleles have increased risk of severe toxicity from systemic fluoropyrimidine chemotherapy. There is a paucity of data regarding risk of toxicity from topical 5\u2010fluorouracil (5\u2010FU) treatment in these patients, leading to inconsistent guideline recommendations for pretreatment testing and topical 5\u2010FU dosing. The objective of this retrospective cohort study was to investigate whether <jats:italic>DPYD<\/jats:italic> variant allele carriers have increased risk of toxicity from topical 5\u2010FU. Treatment and toxicity data were retrospectively abstracted from the electronic medical records. Genotypes for the five <jats:italic>DPYD<\/jats:italic> variants that are associated with increased toxicity from systemic fluoropyrimidine chemotherapy (<jats:italic>DPYD*2A<\/jats:italic>, <jats:italic>DPYD*13<\/jats:italic>, <jats:italic>DPYD p.D949V<\/jats:italic>, <jats:italic>DPYD HapB3<\/jats:italic>, and <jats:italic>DPYD p.Y186C<\/jats:italic>) were collected from a genetic data repository. Incidence of grade 3+ (primary end point) and 1+ (secondary end point) toxicity was compared between <jats:italic>DPYD<\/jats:italic> variant carriers vs. wild\u2010type patients using Fisher's exact tests. The analysis included 201 patients, 7% (14\/201) of whom carried a single <jats:italic>DPYD<\/jats:italic> variant allele. No patients carried two variant alleles or experienced grade 3+ toxicity. <jats:italic>DPYD<\/jats:italic> variant allele carriers did not have a significantly higher risk of grade 1+ toxicity (21.4% vs. 10.2%, odds ratio\u2009=\u20092.40, 95% confidence interval: 0.10\u20132.53, <jats:italic>P<\/jats:italic>\u2009=\u20090.19). Given the low toxicity risk in patients carrying a single <jats:italic>DPYD<\/jats:italic> variant allele, there is limited potential clinical benefit of <jats:italic>DPYD<\/jats:italic> genetic testing prior to topical 5\u2010FU. However, the risk of severe toxicity in patients with complete DPD deficiency remains unknown and topical 5\u2010FU treatment should be avoided in these patients.<\/jats:p>","DOI":"10.1002\/cpt.3131","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T05:08:56Z","timestamp":1702012136000},"page":"452-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Risk of Toxicity From Topical <scp>5\u2010Fluorouracil<\/scp> Treatment in Patients Carrying <i>DPYD<\/i> Variant Alleles"],"prefix":"10.1002","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-1292","authenticated-orcid":false,"given":"Javier","family":"Granados","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan USA"},{"name":"University of Texas at Austin College of Pharmacy  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3162-5498","authenticated-orcid":false,"given":"Amy L.","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4771-5930","authenticated-orcid":false,"given":"N. Lynn","family":"Henry","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Division of Hematology and Oncology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1892-1548","authenticated-orcid":false,"given":"Vaibhav","family":"Sahai","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Division of Hematology and Oncology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-1035","authenticated-orcid":false,"given":"Daniel L.","family":"Hertz","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan USA"},{"name":"Rogel Cancer Center University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.14106"},{"key":"e_1_2_9_2_1","unstructured":"Prescribing information for Efudex\u00ae (fluorouracil topical solutions and cream). Available from: chrome\u2010extension:\/\/efaidnbmnnnibpcajpcglclefindmkaj\/ <https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/016831Orig1s063lbl.pdf> Accessed September 27 2023."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2310\/7750.2013.13143"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.142.6.729"},{"key":"e_1_2_9_5_1","first-page":"2006","article-title":"Life\u2010threatening toxicity in a dihydropyrimidine dehydrogenase\u2010deficient patient after treatment with topical 5\u2010fluorouracil","volume":"5","author":"Johnson M.R.","year":"1999","journal-title":"Clin. 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Accessed December 20 2022."},{"key":"e_1_2_9_25_1","unstructured":"Prescribing information for XELODA\u00ae (Capecitabine) Tablets<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/020896s044s045s046s047s048s049s050s051lbl.pdf>."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T15:44:37Z","timestamp":1708098277000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,18]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/cpt.3131"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3131","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,18]]},"assertion":[{"value":"2023-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}