{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:17:57Z","timestamp":1785860277948,"version":"3.56.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,30]],"date-time":"2017-09-30T00:00:00Z","timestamp":1506729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2018,1,15]]},"abstract":"<jats:p>Fluoropyrimidines are frequently used anti\u2010cancer drugs. It is known that patients with reduced activity of dihydropyrimidine dehydrogenase (DPD), the key metabolic enzyme in fluoropyrimidine inactivation, are at increased risk of developing severe fluoropyrimidine\u2010related toxicity. Upfront screening for DPD deficiency and dose reduction in patients with partial DPD deficiency is recommended and improves patient safety. For patients with complete DPD deficiency, fluoropyrimidine\u2010treatment has generally been discouraged. During routine pretreatment screening, we identified a 59\u2010year\u2010old patient with a sigmoid adenocarcinoma who proved to have a complete DPD deficiency. Genetic analyses showed that this complete absence of DPD activity was likely to be caused by a novel <jats:italic>DPYD<\/jats:italic> genotype, consisting of a combination of amplification of exons 17 and 18 of <jats:italic>DPYD<\/jats:italic> and heterozygosity for <jats:italic>DPYD<\/jats:italic>*2A. Despite absence of DPD activity, the patient was treated with capecitabine\u2010based chemotherapy, but capecitabine dose was drastically reduced to 150 mg once every 5 days (0.8% of original dose). Pharmacokinetic analyses showed that the area under the concentration\u2010time curve (AUC) and half\u2010life of 5\u2010fluorouracil were respectively tenfold and fourfold higher than control values of patients receiving capecitabine 850 mg\/m<jats:sup>2<\/jats:sup>. When extrapolating from the dosing schedule of once every 5 days to twice daily, the AUC of 5\u2010fluorouracil was comparable to controls. Treatment was tolerated well for eight cycles by the patient without occurrence of capecitabine\u2010related toxicity. This case report demonstrates that a more comprehensive genotyping and phenotyping approach, combined with pharmacokinetically\u2010guided dose administration, enables save fluoropyrimidine\u2010treatment with adequate drug exposure in completely DPD deficient patients.<\/jats:p>","DOI":"10.1002\/ijc.31065","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T08:32:53Z","timestamp":1505896373000},"page":"424-430","source":"Crossref","is-referenced-by-count":24,"title":["Capecitabine\u2010based treatment of a patient with a novel <i>DPYD<\/i> genotype and complete dihydropyrimidine dehydrogenase deficiency"],"prefix":"10.1002","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0141-7927","authenticated-orcid":false,"given":"Linda M.","family":"Henricks","sequence":"first","affiliation":[{"name":"Division of Pharmacology and Division of Clinical Pharmacology, Department of Medical Oncology The Netherlands Cancer Institute Amsterdam The 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