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|Title:||Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses|
|Citation:||Pharmacogenomics Journal, 2017; 17(1):21-28|
|JM Campbell, M.D. Stephenson, E Bateman, MDJ Peters, DM Keefe and JM Bowen|
|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.|
|Keywords:||Humans; Neutropenia; Genetic Predisposition to Disease; Diarrhea; Camptothecin; Glucuronosyltransferase; Antineoplastic Agents, Phytogenic; Treatment Outcome; Odds Ratio; Risk Assessment; Risk Factors; Reproducibility of Results; Predictive Value of Tests; Pharmacogenetics; Heterozygote; Homozygote; Phenotype; Polymorphism, Single Nucleotide; Meta-Analysis as Topic; Pharmacogenomic Variants; Pharmacogenomic Testing; Irinotecan; Systematic Reviews as Topic|
|Rights:||© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved|
|Appears in Collections:||Medicine publications|
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