The effect of the UGT1A1∗28 allele on survival after irinotecan-based chemotherapy: A collaborative meta-analysis

M. M. Dias, J. P. Pignon, C. S. Karapetis, V. Boige, B. Glimelius, D. M. Kweekel, Primo N Lara, P. Laurent-Puig, E. Martinez-Balibrea, D. Páez, C. J A Punt, M. W. Redman, G. Toffoli, M. Wadelius, R. A. Mckinnon, M. J. Sorich

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24 Scopus citations

Abstract

To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1∗28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1∗28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1∗28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1∗28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1∗28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1∗28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.

Original languageEnglish (US)
Pages (from-to)424-431
Number of pages8
JournalPharmacogenomics Journal
Volume14
Issue number5
DOIs
StatePublished - Oct 11 2014

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

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    Dias, M. M., Pignon, J. P., Karapetis, C. S., Boige, V., Glimelius, B., Kweekel, D. M., Lara, P. N., Laurent-Puig, P., Martinez-Balibrea, E., Páez, D., Punt, C. J. A., Redman, M. W., Toffoli, G., Wadelius, M., Mckinnon, R. A., & Sorich, M. J. (2014). The effect of the UGT1A1∗28 allele on survival after irinotecan-based chemotherapy: A collaborative meta-analysis. Pharmacogenomics Journal, 14(5), 424-431. https://doi.org/10.1038/tpj.2014.16