title: Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.
abstract: Irinotecan chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. This systematic review of systematic reviews synthesises all meta-analyses on biomarkers for irinotecan toxicity across all genetic models for Asians, Caucasians, low dose, medium/high dose and regimens with and without fluorouracil. False-positive findings are a problem in pharmacogenetics, increasing the importance of systematic reviews. Four systematic reviews that investigated the effect of the polymorphisms UGT1A1*6 and/or*28 on neutropenia or diarrhoea toxicity were included. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for irinotecan-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. UGT1A1*6 and *28 were also related to diarrhoea toxicity; however, at low doses of irinotecan there was evidence that UGT1A1*28 was not. In synthesising the best available evidence, this umbrella systematic review provides a novel reference for clinicians applying personalised medicine and identifies important research gaps.
authors: The Joanna Briggs Institute, Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia.
authors: J M
authors: JM
authors: Campbell
authors: The Joanna Briggs Institute, Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia.
authors: M D
authors: MD
authors: Stephenson
authors: School of Medicine, Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia.
authors: E
authors: E
authors: Bateman
authors: The Joanna Briggs Institute, Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia.
authors: M D J
authors: MD
authors: Peters
authors: School of Medicine, Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia.
authors: D M
authors: DM
authors: Keefe
authors: School of Medicine, Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia.
authors: J M
authors: JM
authors: Bowen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D000077146:Irinotecan; D015201:Meta-Analysis as Topic; D009503:Neutropenia / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics*; D016017:Odds Ratio; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D000078202:Systematic Reviews as Topic; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme