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Journal Article
Meta-Analysis
Review
Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.
Pharmacogenomics Journal 2017 January
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.
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