title: Can inhibiting dihydropyrimidine dehydrogenase limit hand-foot syndrome caused by fluoropyrimidines?
abstract: Hand-foot syndrome (HFS) is a cutaneous adverse event that occurs in some patients treated with fluoropyrimidines. Although it is not life threatening, HFS can severely disrupt the daily lives of patients. HFS appears more frequently with 5-fluorouracil (5-FU) delivered by continuous infusion or with the 5-FU oral derivative capecitabine than with bolus 5-FU therapy. HFS is a leading cause of treatment interruption, dosage reduction, or, even, therapy discontinuation for patients on a capecitabine regimen. Interestingly, addition of a dihydropyrimidine dehydrogenase (DPD) inhibitor, such as uracil, 5-chloro-2,4-dihydroxypyridine, or eniluracil, to the fluoropyrimidine treatment regimen significantly diminishes the incidence of HFS. DPD inhibitors were initially combined with fluoropyrimidines to increase the efficacy of the drugs by impairing the DPD-mediated catabolism of 5-FU. However, with the accumulating findings from clinical trials that show the benefits of DPD inhibition on decreasing the risk of HFS, consideration should be given to changing the recommendations for the treatment of cancer patients with fluoropyrimidines to include DPD inhibitor components as standard therapy.
authors.affiliation: University of North Carolina Schools of Pharmacy and Medicine, Lineberger Comprehensive Cancer Center, Institute for Pharmacogenomics and Individualized Therapy, Chapel Hill, North Carolina 27599-7360, USA.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Yen-Revollo
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005472:Fluorouracil / Q000009:adverse effects*; D005533:Foot Dermatoses / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D006229:Hand Dermatoses / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D006801:Humans; D013577:Syndrome
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil