Come a long way, still a ways to go: from predicting and preventing fluoropyrimidine toxicity to increased efficacy?

[...]450 exonic variants in DPYD with potentially damaging effect have been reported (7). [...]to 5-FU, capecitabine and its downstream metabolites are observed only at low concentrations in plasma due to its intracellular activation, making TDM more challenging (15). [...]pharmacogenetic testing ma...

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Bibliographic Details
Published in:Pharmacogenomics 2018-06, Vol.19 (8), p.689-692
Main Authors: Hamzic, Seid, Amstutz, Ursula, Largiadèr, Carlo R
Format: Article
Language:English
Subjects:
5-FU
Binding sites
Body composition
BSA-based dosing
Cancer therapies
capecitabine
Chemotherapy
Clinical trials
Colorectal cancer
Dehydrogenases
DPYD
Drug dosages
Enzymes
Gender differences
Genotyping
Metabolism
Metabolites
MicroRNAs
Mutation
pharmacogenetics
TDM
Toxicity
Women
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Summary:[...]450 exonic variants in DPYD with potentially damaging effect have been reported (7). [...]to 5-FU, capecitabine and its downstream metabolites are observed only at low concentrations in plasma due to its intracellular activation, making TDM more challenging (15). [...]pharmacogenetic testing may be even more relevant in Cp-treated patients, where routine TDM currently is not feasible. [...]more research is needed to replicate these associations and better understand the impact of these genes and variants on Cp-related toxicities. Besides genotyping, there have been reports on various phenotypic approaches to detect reduced DPD activity pretherapy. [...]no matter which pretherapeutic tests will eventually find their way into routine care, TDM should always complement these methods, at least for the initial cycles, for optimal FP dose individualization.
ISSN:1462-2416
1744-8042
DOI:10.2217/pgs-2018-0040