Authors: Joseph Ciccolini Cedric Mercier Laetitia Dahan Alexandre Evrard JeanChristophe Boyer Karine Richard JeanPhilippe Dales Alain Durand Gerard Milano JeanFrançois Seitz Bruno Lacarelle
Publish Date: 2005/11/15
Volume: 58, Issue: 2, Pages: 272-
Abstract
This report here is the case of a 52yearold male patient who suffered from extremely severe haematological toxicities G4 neutropenia G4 thrombocytopenia while undergoing Xelox Xeloda + Oxaliplatin treatment for his multifocal hepatocarcinoma Despite appropriate supportive treatment his condition quickly deteriorated and led to death It was hypothesized that dihydropyrimidine deshydrogenase DPD gene polymorphism could be at least in part responsible for this fatal outcome To test this hypothesis both phenotypic and genotypic studies were undertaken and fully confirmed the DPDdeficient status of this patient Uracil to dihydrouracil ratio in plasma was evaluated as a surrogate marker for DPD deficiency and showed values out of the range previously recorded from a reference nontoxic population Interestingly the canonical IVS14+1GA single nucleotide polymorphism usually associated with the most severe toxicities reported with 5fluorouracil 5FU was not found in this patient but further investigations showed instead a heterozygosity for the 1896CT mutation located in the exon 14 of the DPYD gene Taken together the data strongly suggest for the first time that a toxicdeath case after capecitabinecontaining protocol could be at least in part linked with a DPDdeficiency syndrome The case reported here warrants therefore systematic detection of patients at risk including when oral capecitabine is scheduled
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