{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:23:27Z","timestamp":1793993007852,"version":"4.8.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the<jats:italic>DPYD<\/jats:italic>gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The<jats:italic>DPYD-<\/jats:italic>gene activity score, determined by four<jats:italic>DPYD<\/jats:italic>variants, predicts DPD activity and can be used to optimize an individual\u2019s starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on<jats:italic>DPYD<\/jats:italic>genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score,<jats:italic>DPYD<\/jats:italic>genotyping is considered \u201cessential\u201d, therefore directing<jats:italic>DPYD<\/jats:italic>testing prior to initiating fluoropyrimidines.<\/jats:p>","DOI":"10.1038\/s41431-019-0540-0","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T18:03:02Z","timestamp":1574186582000},"page":"508-517","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":218,"title":["Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene\u2013drug interaction of DPYD and fluoropyrimidines"],"prefix":"10.1038","volume":"28","author":[{"given":"Carin A. T. 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