This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yen-Revollo, J. L. Articles by McLeod, H. L. Search for Related Content PubMed PubMed Citation Articles by Yen-Revollo, J. L. Articles by McLeod, H. L. Related Collections Therapeutics and Targets: Pharmacology and Toxicology Clinical Research Clinical Research: Clinical Trials

Can Inhibiting Dihydropyrimidine Dehydrogenase Limit Hand-Foot Syndrome Caused by Fluoropyrimidines?

Authors' Affiliation: University of North Carolina Schools of Pharmacy and Medicine, Lineberger Comprehensive Cancer Center, and University of North Carolina Institute for Pharmacogenomics and Individualized Therapy, Chapel Hill, North Carolina

Requests for reprints: Howard L. McLeod, Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Campus Box 7360, 3203 Kerr Hall, Chapel Hill, NC 27599-7360. Phone: 919-966-0512; Fax: 919-962-0644; E-mail: hmcleod{at}unc.edu.

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.

This article has been cited by other articles:

				E. Casado, P. Pfeiffer, J. Feliu, M. Gonzalez-Baron, L. Vestermark, and H. A. Jensen UFT (tegafur-uracil) in rectal cancer Ann. Onc., April 1, 2008; (2008) mdn067v1. [Abstract] [Full Text] [PDF]

				G. C. Prendergast Cancer Management Hatches New Research Problems Cancer Reviews Online Content, February 1, 2008; 2008(2): 3 - 3. [Full Text] [PDF]