Source:http://linkedlifedata.com/resource/pubmed/id/17038885
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2006-10-13
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pubmed:abstractText |
Dihydropyrimidine dehydrogenase (DPD) deficiency leads to dramatic overexposure to fluorouracil (5-FU), resulting in a potentially lethal outcome in patients treated with standard doses. The aim of this study was to validate, in a routine clinical setting, a simple and rapid method to determine the DPD status in a subset of cancer patients, all presenting with life-threatening toxicities following 5-FU or capecitabine intake. In this study, 80 out of 615 patients (13%) suffered severe toxicities, including 5 lethal ones (0.8%), during or after chemotherapy with a fluoropyrimidine drug. Patients with severe toxicities were treated with 5-FU (76 patients) or capecitabine-containing protocols (4 patients). Simplified uracil to di-hydrouracil (U/UH2) ratio determination in plasma was retrospectively performed in these 80 patients, as a surrogate marker of DPD activity. When possible, 5-FU Css determination was performed, and screenings for the canonical IVS14+1G>A mutation were systematically carried out. Comparison of the U/UH2 ratios with a reference, non-toxic population, showed abnormal values suggesting impaired DPD activity in 57 out of the 80 toxic patients (71%) included in this study, and in 4 out of 5 patients (80%) with a fatal outcome. Similarly, drug exposures up to 15 times higher than the range observed in the non-toxic population were also observed. Importantly, no IVS14+1G>A mutation was found in these patients, including those displaying the most severe or lethal toxicities. These data warrant systematic detection of DPD-deficient patients prior to fluoropyrimidine administration, including when oral capecitabine (Xeloda) is scheduled. Finally, the simplified methodology presented here proved to be a low cost and rapid way to identify routinely patients at risk of toxicity with 5-FU or capecitabine.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0163-4356
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pubmed:author |
pubmed-author:BlanquicettCarmeloC,
pubmed-author:BlesiusAuroreA,
pubmed-author:BoyerJean-ChristopheJC,
pubmed-author:CiccoliniJosephJ,
pubmed-author:DahanLaetitiaL,
pubmed-author:DuffaudFlorenceF,
pubmed-author:DurandAlainA,
pubmed-author:EvrardAlexandreA,
pubmed-author:FavreRogerR,
pubmed-author:LacarelleBrunoB,
pubmed-author:MercierCédricC,
pubmed-author:MilanoGérardG,
pubmed-author:RichardKarineK,
pubmed-author:SeitzJean-FrançoisJF
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pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
678-85
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pubmed:meshHeading |
pubmed-meshheading:17038885-Adult,
pubmed-meshheading:17038885-Aged,
pubmed-meshheading:17038885-Antimetabolites, Antineoplastic,
pubmed-meshheading:17038885-Chromatography, High Pressure Liquid,
pubmed-meshheading:17038885-Dihydrouracil Dehydrogenase (NADP),
pubmed-meshheading:17038885-Drug Monitoring,
pubmed-meshheading:17038885-Female,
pubmed-meshheading:17038885-Fluorouracil,
pubmed-meshheading:17038885-Humans,
pubmed-meshheading:17038885-Male,
pubmed-meshheading:17038885-Middle Aged,
pubmed-meshheading:17038885-Neoplasms,
pubmed-meshheading:17038885-Phenotype,
pubmed-meshheading:17038885-Retrospective Studies
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pubmed:year |
2006
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pubmed:articleTitle |
A rapid and inexpensive method for anticipating severe toxicity to fluorouracil and fluorouracil-based chemotherapy.
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pubmed:affiliation |
Clinical Pharmacokinetics Department, La Timone University Hospital, Marseille, France.
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pubmed:publicationType |
Journal Article
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