The dihydrouracil/uracil ratios in plasma and toxicities of 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer patients

Chemotherapy. 2007;53(2):127-31. doi: 10.1159/000099984. Epub 2007 Feb 16.

Abstract

Background: This study was designed to measure the dihydrouracil (UH(2))/uracil (U) ratio in plasma as a surrogate marker for dihydropyrimidine dehydrogenase (DPD) activity and to investigate the relationships of the UH(2)/U ratios in plasma with the toxicities of 5-fluorouracil (5-FU)-based adjuvant chemotherapy and 5-FU plasma concentrations in colorectal cancer patients.

Methods: Thirty colorectal cancer patients received adjuvant chemotherapy of leucovorin plus 5-FU after operations. The concentrations of UH(2), U and 5-FU were assayed by the high-performance liquid chromatography method. The relationships of the UH(2)/U ratios with the 5-FU toxicities and 5-FU plasma concentrations were analyzed.

Results: There was a negative relationship between the UH(2)/U ratios and 5-FU plasma concentrations (p <0.001). 5-FU toxicities had a negative correlation with the UH(2)/U ratios and a positive correlation with 5-FU plasma concentrations (p < 0.05).

Conclusion: The UH(2)/U ratio in plasma has close correlations with the 5-FU plasma concentration and 5-FU toxicity during chemotherapy, which may highlight the theoretical base of individual therapy for patients with colorectal cancer.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / therapeutic use
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / drug therapy
  • Female
  • Fluorouracil / adverse effects*
  • Fluorouracil / pharmacokinetics
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Uracil / analogs & derivatives*
  • Uracil / blood*
  • Vitamin B Complex / therapeutic use

Substances

  • Antimetabolites, Antineoplastic
  • dihydrouracil
  • Vitamin B Complex
  • Uracil
  • Leucovorin
  • Fluorouracil