{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:30:05Z","timestamp":1773037805884,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001537","name":"University of Auckland","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001537","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>Inherited dihydropyrimidine dehydrogenase (DPD) deficiency is a risk factor for severe 5-fluorouracil toxicity. We report a phenotyping approach (thymine challenge test) to prospectively determine DPD activity and the association with severe adverse events.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The primary aim of this prospective study was to determine whether a thymine challenge test could prospectively identify patients at risk of severe toxicity from treatment with 5-fluorouracil\/capecitabine in combination chemotherapy schedules or monotherapy. The focus was prediction of those at risk of \u2265\u2009grade 3 gastrointestinal toxicity. DPD activity was determined from the thymine\/dihydrothymine (THY\/DHT) ratio measured in a urine sample after a thymine test dose (250\u00a0mg, oral).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of the 166 patients, 11.7% had severe diarrhoea\/mucositis. The THY\/DHT ratio was not significantly different in these individuals compared to those with minimal toxicity. However, <jats:italic>post hoc<\/jats:italic> analysis found decreased DPD activity in those who had non-gastrointestinal toxicity, most notably grade\u2009\u2265\u20092 Hand-Foot syndrome (<jats:italic>p<\/jats:italic>\u2009=\u20090.001).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The data do not support our primary hypothesis that this phenotyping approach would discriminate those at risk of severe\/life-threatening gastrointestinal toxicity. The clinical factors which influence gastrointestinal toxicity, particularly in patients receiving CAPOX require further investigation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical trial registration<\/jats:title>\n            <jats:p>ACTRN 12,617,001,109,392 registered 28\/07\/2017.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00280-025-04804-6","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T04:59:04Z","timestamp":1755493144000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A thymine-challenge test to prospectively evaluate dihydropyrimidine dehydrogenase activity for risk of severe 5-fluorouracil-induced gastrointestinal toxicity"],"prefix":"10.1007","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-5368","authenticated-orcid":false,"given":"Nuala","family":"Helsby","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3821-789X","authenticated-orcid":false,"given":"Katrina","family":"Sharples","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6498-6222","authenticated-orcid":false,"given":"Yu Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3115-8244","authenticated-orcid":false,"given":"David","family":"Porter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4951-3539","authenticated-orcid":false,"given":"Kathryn","family":"Burns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5984-1280","authenticated-orcid":false,"given":"Soo Hee","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-4593","authenticated-orcid":false,"given":"Sarah","family":"Benge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7933-303X","authenticated-orcid":false,"given":"Sanjeev","family":"Deva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-1611","authenticated-orcid":false,"given":"Ben","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6150-709X","authenticated-orcid":false,"given":"Christopher","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"North","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8118-8954","authenticated-orcid":false,"given":"R. 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