Genotype-guided fluoropyrimidine dosing: ready for implementation

More than 20 years have passed since dihydropyrimidine dehydrogenase (DPD; encoded by the gene DPYD) deficiency was first described as a pharmacogenetic syndrome, which puts patients with reduced activity of this key catabolic enzyme at risk of toxicity from fluoropyrimidine-based chemotherapy.1 Mor...

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Bibliographic Details
Published in:The lancet oncology 2018-11, Vol.19 (11), p.1421-1422
Main Authors: Amstutz, Ursula, Largiadèr, Carlo R
Format: Article
Language:English
Subjects:
Cancer therapies
Chemotherapy
Drug dosages
Enzymes
Genotype & phenotype
Genotypes
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Summary:More than 20 years have passed since dihydropyrimidine dehydrogenase (DPD; encoded by the gene DPYD) deficiency was first described as a pharmacogenetic syndrome, which puts patients with reduced activity of this key catabolic enzyme at risk of toxicity from fluoropyrimidine-based chemotherapy.1 More recently, understanding of the effect of DPYD variants on the risk of fluoropyrimidine-related toxicity has improved immensely. [...]this reduction was insufficient, as indicated by an increased proportion of National Cancer Institute Common Terminology Criteria for Adverse Events at grade 3 or worse in these patients compared with non-carriers receiving standard-dose fluoropyrimidine (for c.1236: 20 [39%] of 51 carriers, for c.2846: eight [47%] of 17 carriers). [...]therapy cessation because of toxicity might adversely affect treatment effectiveness. [...]the positive effect of genotype-guided fluoropyrimidine dosing on these outcomes clearly shows an overall clinical benefit.
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(18)30744-7