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 Citations (Scopus)

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
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Dihydropyrimidine Dehydrogenase Deficiency
Dihydrouracil Dehydrogenase (NADP)
Fluorouracil
Toxicity
Enzyme activity
Enzymes
Therapeutics
Mucositis
Agranulocytosis
Patient treatment
Pharmacogenetics
Ataxia
Diarrhea
Cross-Sectional Studies

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

@article{c6aa0d47ecc84c6a8b5aa7150d6390a8,
title = "Importance of dihydropyrimidine dehydrogenase (DPD) deficiency in patients exhibiting toxicity following treatment with 5-fluorouracil",
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.",
author = "Johnson, {Martin R.} and Diasio, {Robert B}",
year = "2001",
doi = "10.1016/S0065-2571(00)00011-X",
language = "English (US)",
volume = "41",
pages = "151--157",
journal = "Advances in Biological Regulation",
issn = "2212-4926",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Importance of dihydropyrimidine dehydrogenase (DPD) deficiency in patients exhibiting toxicity following treatment with 5-fluorouracil

AU - Johnson, Martin R.

AU - Diasio, Robert B

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034984031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034984031&partnerID=8YFLogxK

U2 - 10.1016/S0065-2571(00)00011-X

DO - 10.1016/S0065-2571(00)00011-X

M3 - Article

C2 - 11384742

AN - SCOPUS:0034984031

VL - 41

SP - 151

EP - 157

JO - Advances in Biological Regulation

JF - Advances in Biological Regulation

SN - 2212-4926

ER -