{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:55:44Z","timestamp":1791262544236,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>5\u2010fluorouracil (5\u2010FU) is catabolized by dihydropyrimidine dehydrogenase (DPD). DPD deficiency can trigger life\u2010threatening toxicities, and pretesting DPD is increasingly recommended. Here, we investigated the impact of upfront DPD testing on treatment strategy, that is, whether DPD status influences physicians' choice to use 5\u2010FU or not, and if so, whether to maintain standard dosage or reduce it.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a non\u2010interventional, observational study of 525 adult patients likely to be treated with 5\u2010FU. Upfront DPD status was determined by measuring plasma uracil. Multivariate logistic regression was then used to investigate the factors influencing treatment strategies. A further analysis was then performed on a subset of 419 fit patients eligible for 5\u2010FU. Finally, we studied the impact of adaptive dosing on clinical outcomes (efficacy and toxicity) in the 374 patients who received 5\u2010FU eventually.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DPD testing identified 392 extensive (EM; 74.7%), 78 poor (PM; 14.8%), and 55 ultra\u2010rapid metabolizers (UM; 10.5%). Multivariate analyses identified performance status (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), DPD status (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), age (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004), metastatic stage (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) and history of prior 5\u2010FU treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) as factors influencing treatment strategy. PM were more likely to be treated without 5\u2010FU (22%) than EM (3%) or UM (10%) patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Similarly, of those treated with 5\u2010FU, 100% of PM had a dose reduction, compared to 9% and 25% of EM and UM patients, respectively (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). No difference in efficacy (response rate: 51.6%, progression\u2010free survival: 14.7\u2009months) and safety (severe toxicities: 4.3%) was found, regardless of the DPD status and subsequent dose adaptation, but reduced survival was observed in patients for whom 5\u2010FU was excluded.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Upfront DPD testing has a strong impact on treatment strategies, and subsequent adaptive dosing limits the risk for severe toxicities without compromising efficacy in real\u2010world patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72178","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:34:24Z","timestamp":1789191264000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Upfront\n                    <scp>DihydroPyrimidine<\/scp>\n                    Dehydrogenase (\n                    <scp>DPD<\/scp>\n                    ) Testing on the Therapeutic Management of Patients Scheduled for 5\u2010\n                    <scp>FU<\/scp>"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6820-9859","authenticated-orcid":false,"given":"Govind","family":"Kallee","sequence":"first","affiliation":[{"name":"PRISM, Biogenop\u00f4le La Timone University Hospital of Marseille, APHM  Marseille France"},{"name":"COMPO, Inserm U1068, CRCM, Aix Marseille Univ, Institut Paoli Calmettes, INRIA Sophia Antipolis &amp; Marseille  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Salas","sequence":"additional","affiliation":[{"name":"Medical Oncology La Timone University Hospital of Marseille, APHM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Milano","sequence":"additional","affiliation":[{"name":"Scientific Direction, Centre Antoine Lacassagne  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2057-3557","authenticated-orcid":false,"given":"Florence","family":"Duffaud","sequence":"additional","affiliation":[{"name":"Medical Oncology La Timone University Hospital of Marseille, APHM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Dahan","sequence":"additional","affiliation":[{"name":"Digestive Oncology La Timone University Hospital of Marseille, APHM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-3410","authenticated-orcid":false,"given":"Joseph","family":"Ciccolini","sequence":"additional","affiliation":[{"name":"PRISM, Biogenop\u00f4le La Timone University Hospital of Marseille, APHM  Marseille France"},{"name":"COMPO, Inserm U1068, CRCM, Aix Marseille Univ, Institut Paoli Calmettes, INRIA Sophia Antipolis &amp; Marseille  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101681.1998.tb02339"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.20517\/cdr.2018.006"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2016.08.002"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/07357900500524702"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2010.n.033"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14133207"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.94"},{"key":"e_1_2_12_9_1","unstructured":"Haute Autorit\u00e9 de Sant\u00e9 \u201cRecommendations to Prevent Certain Severe Toxicities of Fluoropyrimidine Chemotherapy \u201dPress Release. 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