{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:10:59Z","timestamp":1791414659889,"version":"4.3.3"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,28]],"date-time":"2015-11-28T00:00:00Z","timestamp":1448668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>5\u2010FU is the backbone of most regimens in digestive oncology. Administration of standard 5\u2010FU leads to 15\u201330% of severe side effects, and lethal toxicities are regularly reported with fluoropyrimidine drugs. Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome responsible for most cases of life\u2010threatening toxicities upon 5\u2010FU intake, and pre\u2010treatment checking for DPD status should help to reduce both incidence and severity of side effects through adaptive dosing strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have used a simple method for rapidly establishing the DPD phenotype of patients with cancer and used it prospectively in 59 routine patients treated with 5\u2010FU\u2010based therapy for digestive cancers. No patient with total DPD deficiency was found but 23% of patients exhibited poor metabolizer phenotype, and one patient was phenotyped as profoundly deficient. Consequently, 5\u2010FU doses in poor metabolizer patients were cut by an average 35% as compared with non deficient patients (2390\u00a0\u00b1\u00a01225\u00a0mg <jats:italic>vs<\/jats:italic>. 3653\u00a0\u00b1\u00a01371\u00a0mg, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.003, <jats:italic>t<\/jats:italic>\u2010test).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Despite this marked reduction in 5\u2010FU dosing, similar efficacy was achieved in the two subsets (clinical benefit: 40 <jats:italic>vs<\/jats:italic>. 43%, stable disease: 40 <jats:italic>vs<\/jats:italic>. 37%, progressive disease: 20% in both subsets, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.893, Pearson's chi\u2010square). No difference in toxicities was observed (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.104, Fisher's exact test). Overall, only 3% of early severe toxicities were recorded, a value markedly lower than the 15\u201030% ones usually reported with 5\u2010FU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This feasibility study shows how simplified DPD\u2010based adaptive dosing of 5\u2010FU can reduce sharply the incidence of treatment\u2010related severe toxicities while maintaining efficacy as part of routine clinical practice in digestive oncology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12790","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T10:33:15Z","timestamp":1442917995000},"page":"124-130","source":"Crossref","is-referenced-by-count":47,"title":["Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase\u2010driven adaptive dosing of 5\u2010FU in patients with digestive cancer"],"prefix":"10.1111","volume":"81","author":[{"given":"Manon","family":"Launay","sequence":"first","affiliation":[{"name":"Laboratoire de Pharmacocin\u00e9tique La Timone University Hospital of Marseille  Marseille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Dahan","sequence":"additional","affiliation":[{"name":"Digestive Oncology Unit La Timone University Hospital of Marseille  Marseille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Duval","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacocin\u00e9tique La Timone University Hospital of Marseille  Marseille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Rodallec","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacocin\u00e9tique La Timone University Hospital of Marseille  Marseille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rard","family":"Milano","sequence":"additional","affiliation":[{"name":"Oncopharmacology Unit Centre Antoine Lacassagne  Nice"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Duluc","sequence":"additional","affiliation":[{"name":"Digestive Oncology Unit La Timone University Hospital of Marseille  Marseille"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Lacarelle","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacocin\u00e9tique La Timone University Hospital of Marseille  Marseille"},{"name":"SMARTc Unit U911 Cro2 Aix\u2010Marseille Univ.  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ciccolini","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacocin\u00e9tique La Timone University Hospital of Marseille  Marseille"},{"name":"SMARTc Unit U911 Cro2 Aix\u2010Marseille Univ.  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Francois","family":"Seitz","sequence":"additional","affiliation":[{"name":"Digestive Oncology Unit La Timone University Hospital of Marseille  Marseille"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2011.118"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2010.n.033"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.COC.0000017526.55135.6D"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.11.2248"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2006.n.047"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2013.25"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.3934"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010396710"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000245771.82720.c7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-010-1282-4"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2003.12.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.09.009"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03307.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.11.72"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.210"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13167-015-0039-x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.116"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/827989"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.51.1857"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2766"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16048884"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1998.00050.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.126"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-011-1661-5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2553-2"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0139-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.09.009"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1529"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802612803531414"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03257473"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.12790","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.12790","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T17:42:12Z","timestamp":1696354932000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.12790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,28]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1111\/bcp.12790"],"URL":"https:\/\/doi.org\/10.1111\/bcp.12790","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,28]]}}}