UGT1A1*1/*28 and *1/*6 genotypes have no effects on the efficacy and toxicity of FOLFIRI in Japanese patients with advanced colorectal cancer

Cancer Chemother Pharmacol. 2011 Aug;68(2):279-84. doi: 10.1007/s00280-010-1485-8. Epub 2010 Oct 19.

Abstract

Purpose: Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients.

Methods: Patients with advanced colorectal cancer who received irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) as first-line therapy were divided into two groups: those with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Efficacy and toxicity were compared between these groups retrospectively.

Results: Forty-two patients (24 *1/*1 and 18 *1/*6 or *1/*28) were evaluated. The response rate was 48% in *1/*1 group and 56% in *1/*6 or *1/*28 group (P = 0.847). Median progression-free survival was 8.6 months in *1/*1 group and 8.5 months in *1/*6 or *1/*28 group (P = 0.888). No hematologic or non-hematologic toxic effects were clearly related to UGT1A1*1/*6 or *1/*28 during the first cycle or throughout the entire course of chemotherapy.

Conclusions: There were no significant differences in the efficacy or toxicity of FOLFIRI between patients with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Our results suggest that patients with the latter genotypes can receive FOLFIRI at the same dose of irinotecan as those with the UGT1A1*1/*1 genotype receive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biotransformation / genetics
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Genetic Association Studies
  • Glucuronosyltransferase / genetics*
  • Heterozygote
  • Humans
  • Irinotecan
  • Japan
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Genetic*
  • Prodrugs / administration & dosage
  • Prodrugs / adverse effects
  • Prodrugs / pharmacokinetics
  • Prodrugs / therapeutic use*
  • Retrospective Studies
  • Survival Analysis
  • Topoisomerase I Inhibitors / administration & dosage
  • Topoisomerase I Inhibitors / adverse effects
  • Topoisomerase I Inhibitors / pharmacokinetics
  • Topoisomerase I Inhibitors / therapeutic use*

Substances

  • Prodrugs
  • Topoisomerase I Inhibitors
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol