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Dihydropyrimidine dehydrogenase deficiency: a pharmacogenetic defect causing severe adverse reactions to 5-fluorouracil-based chemotherapy.

AbstractPURPOSE/OBJECTIVES:
To describe the pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients with cancer to potentially lethal adverse reactions following 5-fluorouracil (5-FU)-based chemotherapy.
DATA SOURCES:
Published articles, abstracts, and conference proceedings.
DATA SYNTHESIS:
Genetic deficiencies in DPD, the rate-limiting enzyme responsible for 5-FU catabolism, may occur in 3% or more of patients with cancer putting them at increased risk for unusually severe adverse reactions (e.g., diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity) to standard doses of 5-FU. Diagnosis of DPD deficiency must be confirmed by specialized laboratory tests. The principle treatment for DPD-deficient patients with severe acute 5-FU reactions is supportive care; however, the administration of thymidine potentially may reverse severe 5-FU-induced neurologic symptoms such as encephalopathy and coma.
CONCLUSIONS:
Early recognition of this serious pharmacogenetic syndrome may allow for the modification of future chemotherapy, thus avoiding further life-threatening toxicities.
IMPLICATIONS FOR NURSING PRACTICE:
Nurses must understand the pharmacology, mechanism of action, clinical presentation, potentially lethal risks, and traumatic psychosocial stresses experienced by DPD-deficient patients with cancer receiving 5-FU therapy in order to develop timely interventions and alternative plans of care.
AuthorsG B Morrison, A Bastian, T Dela Rosa, R B Diasio, C H Takimoto
JournalOncology nursing forum (Oncol Nurs Forum) 1997 Jan-Feb Vol. 24 Issue 1 Pg. 83-8 ISSN: 0190-535X [Print] United States
PMID9007910 (Publication Type: Case Reports, Journal Article, Review)
Chemical References
  • Antimetabolites, Antineoplastic
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil
Topics
  • Adult
  • Antimetabolites, Antineoplastic (adverse effects, metabolism)
  • Carcinoma, Hepatocellular (drug therapy, secondary)
  • Dihydrouracil Dehydrogenase (NADP)
  • Female
  • Fluorouracil (adverse effects, metabolism)
  • Humans
  • Liver Neoplasms (drug therapy, pathology)
  • Male
  • Metabolism, Inborn Errors (complications)
  • Middle Aged
  • Neoplasms (drug therapy)
  • Oxidoreductases (deficiency)
  • Pleural Neoplasms (drug therapy, secondary)
  • Severity of Illness Index

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