UGT1A1*28 and other UGT1A polymorphisms as determinants of irinotecan toxicity

P. Biason, S. Masier, Giuseppe Toffoli

Research output: Contribution to journalArticlepeer-review

Abstract

Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. Neutropenia and diarrhea are the dose-limiting toxicities. Genetic variations of proteins involved in irinotecan metabolism and transport have been considered in the development of irinotecan toxicity. In particular, polymorphisms affecting UDP- glucuronosyltransferase isoform 1A1 (UGT1A1) expression or activity are being investigated. Among these, UGT1A1*28 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A1*28 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage. Further prospective studies are required to reach a personalization of chemotherapy with irinotecan.

Original languageEnglish
Pages (from-to)158-165
Number of pages8
JournalJournal of Chemotherapy
Volume20
Issue number2
Publication statusPublished - Apr 2008

Keywords

  • APC: 7-ethyl-10-[4-N-(5-amino pentanoic acid)-1-piperidino]- carbonyloxycamptothecin
  • CRC: Colorectal cancer
  • hCE: Human carboxylesterases
  • NPC: 7-ethyl-10-[4-(1-piperidino)-1-amino]- carbonyloxycamptothecin
  • SN38: 7-ethyl-10-hydroxycamptothecin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Microbiology (medical)
  • Medicine(all)

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