Abstract
In The Lancet Oncology, Didier Meulendijks and colleagues report the findings from their meta-analysis of eight studies of DPYD genetic variants as predictors of fluoropyrimidine-induced severe toxicity. 1 Meulendjiks D Henricks LM Sonke GS et al. Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015; (published online Oct 23.)http://dx.doi.org/10.1016/S1470-2045(15)00286-7 Google Scholar In Meulendijks and colleagues' meta-analysis of 7365 patients, DPYD c.1679T>G and c.1236G>A/HapB3 were significantly associated with fluoropyrimidine-associated toxicity (adjusted relative risk 4·40, 95% CI 2·08–9·30, p<0·0001; and 1·59, 1·29–1·97, p<0·0001, respectively). The investigators noted consistent associations of c.1679T>G and c.1236G>A/HapB3 with gastrointestinal and haematological toxicities, but not with hand-foot syndrome. Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome resulting in an inability or impaired ability in some patients to detoxify fluorouracil in the liver. Consequently, DPD-deficient patients will have life-threatening toxicities with standard doses of fluorouracil. Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient dataDPYD variants c.1679T>G and c.1236G>A/HapB3 are clinically relevant predictors of fluoropyrimidine-associated toxicity. Upfront screening for these variants, in addition to the established variants DPYD*2A and c.2846A>T, is recommended to improve the safety of patients with cancer treated with fluoropyrimidines. Full-Text PDF
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