About: Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer     Goto   Sponge   NotDistinct   Permalink

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  • The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit.
  • The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit. (en)
Title
  • Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer
  • Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer (en)
skos:prefLabel
  • Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer
  • Predictors of Irinotecan Toxicity and Efficacy in Treatment of Metastatic Colorectal Cancer (en)
skos:notation
  • RIV/00179906:_____/12:10133953!RIV13-MZ0-00179906
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I
http://linked.open...iv/cisloPeriodika
  • 4
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
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  • 161064
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  • RIV/00179906:_____/12:10133953
http://linked.open...riv/jazykVysledku
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  • Diarrhea; Neutropenia; Pharmacogenetics; UGT1A1*28; SN-38; Irinotecan (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • CZ - Česká republika
http://linked.open...ontrolniKodProRIV
  • [8698CDC4FD19]
http://linked.open...i/riv/nazevZdroje
  • Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Kralove
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 55
http://linked.open...iv/tvurceVysledku
  • Filip, Stanislav
  • Grim, Jiří
  • Paulík, Adam
issn
  • 1211-4286
number of pages
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