Importance of dihydropyrimidine dehydrogenase (DPD) deficiency in patients exhibiting toxicity following treatment with 5-fluorouracil

Martin R. Johnson, Robert B. Diasio

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Each year, there are an increasing number of case reports describing severe toxicity (including death) to treatment with 5-fluorouracil (5-FU) resulting from dihydropyrimidine dehydrogenase (DPD) deficiency. Despite these studies, the prevalence and overall clinical significance of this pharmacogenetic disease remains unclear. We examined DPD enzyme activity in a group of 103 cancer patients undergoing treatment with 5-FU who developed unanticipated toxicity including death, mucositis, granulocytopenia, diarrhea, neuropathy and ataxia. Forty-four patients (43%) demonstrated profound (≤0.024nmol/min/mg, n=12) or partial (≤ 0.064nmol/min/mg, n=32) DPD enzyme deficiency while 59 patients (57%) demonstrated normal DPD enzyme activity (≥ 0.064 nmol/min/mg). These data support the conclusions that (a) profound and partial DPD deficiency has a significant role (43%) in patients who develop life threatening toxicity following administration of routine doses of 5-FU; (b) partial DPD deficiency appears more frequent than profound deficiency (31% versus 12%, respectively) and; (c) 57% of these patients demonstrated normal DPD enzyme activity suggesting that the mechanism responsible for a large population of patients exhibiting severe toxicity to 5-FU remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)151-157
Number of pages7
JournalAdvances in Enzyme Regulation
Volume41
Issue number1
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

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