Relationship between plasma concentrations of 5-fluorouracil and 5-fluoro-5,6-dihydrouracil and toxicity of 5-fluorouracil infusions in cancer patients

Antonello Di Paolo, Toni Ibrahim, Romano Danesi, Marco Maltoni, Francesca Vannozzi, Emanuela Flamini, Wainer Zoli, Dino Amadori, Mario Del Tacca

Research output: Contribution to journalArticlepeer-review

Abstract

This study investigated the relationship among the pharmacokinetics of 5-fluorouracil (5-FU) and 5-fluoro-5,6-dihydrouracil (5-FDHU); the activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells; and treatment-related toxicity in 26 patients with surgically resected colorectal cancer treated with short daily infusions of 5-FU adjuvant chemotherapy, each cycle consisting of 5 consecutive days every 4 weeks. After the first chemotherapeutic cycle, severe stomatitis and diarrhea occurred in 5 patients and were related to the variations in the systemic disposition of the drug rather than to DPD activity. These patients showed a significant decrease in 5-FU clearance, and an increase in the 5-FU/5-FDHU area under the time-concentration curve (AUC) ratio, as compared with patients who experienced mild toxicities, whereas a low DPD activity was observed in only 2 patients. In conclusion, the results of this study demonstrate that the alterations in 5-FU and 5-FDHU pharmacokinetics are related to severe toxicities in patients treated with short intravenous infusion of 5-FU.

Original languageEnglish
Pages (from-to)588-593
Number of pages6
JournalTherapeutic Drug Monitoring
Volume24
Issue number5
DOIs
Publication statusPublished - Oct 2002

Keywords

  • 5-Fluorouracil
  • Adjuvant chemotherapy
  • Colorectal cancer
  • Dihydropyrimidine dehydrogenase
  • Toxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

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