Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency

Nadine Shehata, Alan Pater, Shou Ching Tang

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

5-Fluorouracil (5-FU) is an analogue of pyrimidine nucleosides that is widely used in the treatment of head and neck, breast, ovarian, and colon cancer. Stomatitis, diarrhea, dermatitis, and myelosuppression are the main toxicities of 5-FU. A less frequent side effect that is becoming more recognized is neurologic toxicity. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU. DPD deficiency follows an autosomal recessive pattern of inheritance, and its prevalence is estimated to be 3%. Cancer patients who are receiving 5-FU treatment and are DPD deficient can develop severe side effects. The neurologic toxicity can vary from being mild to severe and prolonged. We describe the side effects of 5- FU in a colon cancer patient who suffered severe mucositis, desquamating dermatitis, prolonged myelosuppression, and neurologic toxicity that required admission to the intensive care unit. The patient remained hospitalized for 3 months. Recovery from the side effects was complete 4 months after the last 5-FU treatment. Subsequent testing revealed that this patient has an extremely low level of DPD activity (0.015 nmol/min/mg protein; mean, 0.189 nmol/min/mg protein). Because neurologic toxicity is becoming more recognized and DPD affects the catabolism of 5-FU, we discuss management issues and the use of new DPD inhibitors. We also discuss whether screening for DPD deficiency is warranted to identify patients at risk for severe toxicities from 5-FU treatment.

Original languageEnglish (US)
Pages (from-to)201-205
Number of pages5
JournalCancer Investigation
Volume17
Issue number3
DOIs
StatePublished - 1999

Keywords

  • 5-Fluorouracil
  • Colon cancer chemotherapy
  • Dihydropyrimidine dehydrogenase deficiency
  • Neurotoxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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