{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:08:10Z","timestamp":1789794490214,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anticancer drug 5FU is extensively metabolized by dihydropyrimidine dehydrogenase (DPD), an enzyme with high interindividual variability. Poor metabolizer (PM, i.e., DPD deficient) patients are at risk of life\u2010threatening toxicities. Whether ultra\u2010rapid metabolizer (UM) status could conversely compromise 5FU efficacy remains to be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this real\u2010world study, 352 adult patients treated with a 5FU\u2010containing regimen were screened. Patients were classified as normal (extensive metabolizer, EM), PM, or UM on DPD function based upon baseline plasma uracil monitoring. The impact of DPD status on efficacy and safety endpoints was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients were categorized on DPD as UM (11.9%), EM (75.9%), and PM (12.2%). The response rate was 54.5%, with median PFS and OS of 13.9 and 19\u2009months, respectively. PM patients were treated with an average 13% lower 5FU starting dose. There was no statistical difference in efficacy between UM and other patients. Severe toxicities were observed in less than 5% of patients, an incidence significantly lower than commonly reported with 5FU\u2010containing regimen and was comparable between UM, EM, and PM patients. Our observations suggest that UM status is not associated with the lack of efficacy of 5FU. In addition, upfront DPD testing with adaptive dosing helps to reduce the incidence of severe toxicities, as PM patients on reduced doses did not have more severe toxicities than other patients treated with standard doses, while exhibiting similar efficacy in terms of response rate and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>When upfront DPD screening with adaptive dosing is performed, no difference is observed between UM, EM, and PM patients in terms of efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>#PADSA3GKW7<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/fcp.70035","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T22:20:01Z","timestamp":1751926801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["DPD Ultra\u2010Rapid Metabolizer Status and Efficacy of 5\u2010Fluorouracil Treatment: A Real\u2010World Study"],"prefix":"10.1111","volume":"39","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  Marseille France"},{"name":"COMPO, Inserm U1068 CRCM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Milano","sequence":"additional","affiliation":[{"name":"Centre Antoine Lacassagne  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Duffaud","sequence":"additional","affiliation":[{"name":"Medical Oncology La Timone University Hospital of Marseille  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Dahan","sequence":"additional","affiliation":[{"name":"Digestive Oncology La Timone University Hospital of Marseille  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  Marseille France"},{"name":"COMPO, Inserm U1068 CRCM  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"issue":"3","key":"e_1_2_13_2_1","first-page":"787","article-title":"Tailored Therapy in Patients Treated With Fluoropyrimidines: Focus on the Role of Dihydropyrimidine Dehydrogenase","volume":"2","author":"Merloni F.","year":"2019","journal-title":"Cancer Drug Resistance"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2016.08.002"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600208"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03257473"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph13110416"},{"issue":"10","key":"e_1_2_13_7_1","first-page":"2899","article-title":"Correlation Between Dihydropyrimidine Dehydrogenase Activity in Peripheral Mononuclear Cells and Systemic Clearance of Fluorouracil in Cancer Patients","volume":"52","author":"Fleming R. 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