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

The Pharmacogenomics Journal volume 14, pages 424–431 (2014)Cite this article

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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 A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy.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.

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Author information

Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia

    M M Dias & M J Sorich

  2. Department of Biostatistics and Epidemiology, Meta-analysis Unit, Gustave-Roussy, Villejuif, France

    J-P Pignon

  3. Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia, Australia

    C S Karapetis & R A McKinnon

  4. Department of Oncologic Medicine, Gustave-Roussy, Villejuif, France

    V Boige

  5. Department of Radiology, Section of Oncology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden

    B Glimelius

  6. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, The Netherlands

    D M Kweekel

  7. Davis Comprehensive Cancer Center, University of California, Sacramento, CA, USA

    P N Lara

  8. Unité Mixte de Recherche S775, Institut National de la Santé et de la Recherche Médicale, Université Paris Descartes, Paris, France

    P Laurent-Puig

  9. Laboratori Biologia Molecular del Càncer, Institut Català d’Oncologia, Fundació Institut IGTP, Badalona, Spain

    E Martinez-Balibrea

  10. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    D Páez

  11. Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    C J A Punt

  12. Lung and Cancer Control Committees, Fred Hutchinson Cancer Research Center, Statistical Center: SWOG, Seattle, WA, USA

    M W Redman

  13. Experimental and Clinical Pharmacology Unit, CRO-National Cancer Institute, Aviano, Italy

    G Toffoli

  14. Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden

    M Wadelius

  15. Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, South Australia, Australia

    M J Sorich

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  1. M M Dias
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Dias, M., Pignon, JP., Karapetis, C. et al. The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis. Pharmacogenomics J 14, 424–431 (2014). https://doi.org/10.1038/tpj.2014.16

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