title: Dihydropyrimidine dehydrogenase polymorphisms and fluoropyrimidine toxicity: ready for routine clinical application within personalized medicine?
abstract: Fluoropyrimidines, including 5-fluorouracil (5-FU), are widely used in the treatment of solid tumors and remain the backbone of many combination regimens. Despite their clinical benefit, fluoropyrimidines are associated with gastrointestinal and hematologic toxicities, which often lead to treatment discontinuation. 5-FU undergoes complex metabolism, dihydropyrimidine dehydrogenase (DPD) being the rate-limiting enzyme of inactivation of 5-FU and its prodrugs. Several studies have demonstrated significant associations between severe toxicities by fluoropyrimidines and germline polymorphisms of DPD gene. To date, more than 30 SNPs and deletions have been identified within DPD, the majority of these variants having no functional consequences on enzymatic activity. However, the identification of deficient DPD genotypes may help identify poor-metabolizer patients at risk of developing potentially life-threatening toxicities after standard doses of fluoropyrimidines.
authors.affiliation: Division of Pharmacology, Department of Internal Medicine, University of Pisa, 55, Via Roma, 56126 Pisa, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Del Re
authors.forename: Antonello
authors.initials: A
authors.lastname: Di Paolo
authors.forename: Ron H
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Guido
authors.initials: G
authors.lastname: Bocci
authors.forename: Paolo
authors.initials: P
authors.lastname: Simi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi