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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Alleles
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Biotransformation / genetics
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Camptothecin / administration & dosage
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Camptothecin / adverse effects
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Camptothecin / analogs & derivatives*
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Camptothecin / pharmacokinetics
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Camptothecin / therapeutic use
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / enzymology
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Colorectal Neoplasms / genetics
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Female
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Fluorouracil / administration & dosage
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Fluorouracil / adverse effects
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Fluorouracil / therapeutic use
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Genetic Association Studies
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Glucuronosyltransferase / genetics*
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Heterozygote
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Humans
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Irinotecan
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Japan
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Leucovorin / administration & dosage
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Leucovorin / adverse effects
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Leucovorin / therapeutic use
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Middle Aged
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Neoplasm Staging
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Polymorphism, Genetic*
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Prodrugs / administration & dosage
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Prodrugs / adverse effects
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Prodrugs / pharmacokinetics
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Prodrugs / therapeutic use*
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Retrospective Studies
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Survival Analysis
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Topoisomerase I Inhibitors / administration & dosage
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Topoisomerase I Inhibitors / adverse effects
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Topoisomerase I Inhibitors / pharmacokinetics
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Topoisomerase I Inhibitors / therapeutic use*
Substances
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Prodrugs
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Topoisomerase I Inhibitors
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Irinotecan
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UGT1A1 enzyme
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Glucuronosyltransferase
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Leucovorin
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Fluorouracil
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Camptothecin