Impact of the UGT1A1*28 allele on response to irinotecan: A systematic review and meta-analysis

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    Abstract

    Aim: Pre-emptive irinotecan dose reduction for UGT1A1*28 homozygotes may result in reduced risk of severe neutropenia and diarrhea. However, clinical utility and cost-effectiveness are dependent upon such a dose reduction not impacting irinotecan efficacy. Whether UGT1A1*28 genotype is associated with irinotecan response therefore is an important gap in existing knowledge to inform clinical utility. Materials & methods: A systematic review and meta-analysis was performed to analyze the difference in objective response rate (ORR) between irinotecan-administered cancer patients with different UGT1A1*28 genotypes: *28/*28 (homozygous variant), *1/*28 (heterozygous variant) or *1/*1 (wild-type). The effect of irinotecan dose on the association between UGT1A1*28 and ORR was also assessed. Results: Differences in ORR for either of the genotype comparisons, *28/*28 versus *1/*1 and *1/*28 versus *1/*1, were not statistically significant. Irinotecan dose also did not impact upon ORR differences between UGT1A1 genotype groups. Conclusion: An individual's response to irinotecan is unlikely to be affected by UGT1A1*28 status.

    Original languageEnglish
    Pages (from-to)889-899
    Number of pages11
    JournalPharmacogenomics
    Volume13
    Issue number8
    DOIs
    Publication statusPublished - 1 Jun 2012

    Keywords

    • irinotecan
    • meta-analysis
    • pharmacogenetics
    • response
    • UGT1A1*28

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