{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:06:08Z","timestamp":1779782768812,"version":"3.53.1"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complete dihydropyrimidine dehydrogenase (DPD) deficiency due to homozygous DPYD*2A is a contraindication for fluoropyrimidines because of the extreme risk of life\u2010threatening toxicity. We report a 36\u2010year\u2010old male with metastatic rectal adenocarcinoma and complete DPD deficiency who received ultra\u2010low\u2010dose capecitabine in combination with oxaliplatin and cetuximab. Initial dosing of capecitabine 150\u2009mg on Days 1, 6 and 16 of a 21\u2010day cycle (0.76% of the BSA\u2010based standard regimen) caused Grade 3 mucositis, but further dose reduction to capecitabine 150\u2009mg on Days 1 and 8 of a 21\u2010day cycle (0.50%) improved tolerability. Pharmacokinetic analyses revealed markedly prolonged 5\u2010fluorouracil exposure with undetectable fluoro\u2010\u03b2\u2010alanine (FBAL), consistent with complete DPD deficiency. Despite the minimal dosing, a near\u2010complete metabolic response was achieved after four cycles, enabling surgical resection of residual disease. This case illustrates that carefully individualized ultra\u2010low\u2010dose capecitabine, guided by pharmacokinetics and toxicity monitoring, can provide meaningful clinical benefit in patients with complete DPD deficiency. These findings highlight the therapeutic potential of a precision dosing approach in this rare but clinically challenging setting.<\/jats:p>","DOI":"10.1002\/bcp.70476","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T01:04:38Z","timestamp":1770167078000},"page":"1922-1928","source":"Crossref","is-referenced-by-count":0,"title":["Clinical response to capecitabine in a\n                    <i>DPYD*2A<\/i>\n                    homozygous patient: Case report and therapeutic guidance"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-8937","authenticated-orcid":false,"given":"Michiel A.","family":"Damhof","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology Frisius Medical Center  Leeuwarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-529X","authenticated-orcid":false,"given":"Lisanne N.","family":"van Merendonk","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology The Netherlands Cancer Institute\u2014Antoni van Leeuwenhoek Amsterdam  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco B.","family":"Polee","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Frisius Medical Center  Leeuwarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Bouma","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology Frisius Medical Center  Leeuwarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric N.","family":"van Roon","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology Frisius Medical Center  Leeuwarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin D. R.","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology The Netherlands Cancer Institute\u2014Antoni van Leeuwenhoek Amsterdam  The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Clinical Pharmacy University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Cats","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Division of Medical Oncology The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart A. W.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology The Netherlands Cancer Institute\u2014Antoni van Leeuwenhoek Amsterdam  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"issue":"8","key":"e_1_2_11_2_1","first-page":"2203","article-title":"Clinical pharmacokinetics of 5\u2010fluorouracil and its metabolites in plasma, urine, and bile","volume":"47","author":"Heggie GD","year":"1987","journal-title":"Cancer Res"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03257473"},{"issue":"3","key":"e_1_2_11_4_1","first-page":"768","article-title":"Profound dihydropyrimidine dehydrogenase deficiency resulting from a novel compound heterozygote genotype","volume":"8","author":"Johnson MR","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113308"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201010\u20102209"},{"issue":"8","key":"e_1_2_11_7_1","first-page":"1247","article-title":"The role of IVS14+1 G>a genotype detection in the dihydropyrimidine dehydrogenase gene and pharmacokinetic monitoring of 5\u2010fluorouracil in the individualized adjustment of 5\u2010fluorouracil for patients with local advanced and metastatic colorectal cancer: a preliminary report","volume":"18","author":"Cai X","year":"2014","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.17.00118"},{"issue":"5","key":"e_1_2_11_9_1","first-page":"1149","article-title":"Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5\u2010fluorouracil: frequency of the common IVS14+1G>a mutation causing DPD deficiency","volume":"7","author":"Kuilenburg AB","year":"2001","journal-title":"Clin Cancer Res"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2012.00312"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.911"},{"key":"e_1_2_11_12_1","unstructured":"(EMA) EMA: capecitabine: EPAR\u2014oroduct information Last updated: 31\/03\/2023"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010019\u20100540\u20100"},{"issue":"1","key":"e_1_2_11_14_1","first-page":"S1","article-title":"The concise guide to pharmacology 2021\/22: enzymes","volume":"178","author":"Alexander SPH","year":"2021","journal-title":"Br J Pharmacol"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(18)30686\u20107"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1691\/ph.2023.3001"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31065"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010015\u20102872\u2010y"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010016\u20103054\u20102"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.14464"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12877"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010020\u201000533\u20101"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.11.3537"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70476","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70476","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70476","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:47:33Z","timestamp":1779781653000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/bcp.70476"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70476","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]}}}