Capecitabine
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Severe toxicity and death in a patient with dihydropyrimidine dehydrogenase deficiency: case report A patient [age and sex not stated] started receiving capecitabine 1500mg twice daily for 14 days in a 3 weekly cycle [therapeutic indication not stated]. At day 6, the patient discontinued capecitabine and, on day 7, was hospitalised with severe neutropenia and mucositis. Over the next days, the patient developed severe toxicity and died on day 21. Genome analysis revealed the following heterozygous mutations: IVS14 +1 G > A, 2846 A > T, 1627 A > G, IVS13 +39 C > T, IVS + 40 A > C and IVS18 + 39 G >A. Author comment: "The IVS14 +1 G > A and the 2846 A > T polymorphism are the major contributors resulting in [dihydropyrimidine dehydrogenase]-deficiency, as they lead to complete skipping of exon 14, and interfere directly with cofactor binding or electron transport, respectively. . . [T]he combination of these [single nucleotide polymorphisms] have resulted in several deaths." Deenen MJ, et al. DPYD genome analysis in a patient with lethal capecitabine toxicity. Basic and Clinical Pharmacology and Toxicology 101 (Suppl. 1): 119 801083242 abstr. P181, Sep 2007 [abstract] - Netherlands
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Reactions 20 Oct 2007 No. 1174
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