Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and eniluracil

M. Wasif Saif, Richard H. Wilson, Nancy Harold, Bruce Keith, David S. Dougherty, Jean L Grem

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

5-Fluorouracil (5-FU)-associated neurotoxicity is uncommon; symptoms may occur abruptly or more gradually during the course of chemotherapy. Peripheral neuropathy with 5-FU therapy has only rarely been reported. Two patients treated in a phase I trial of oral 5-FU, leucovorin and eniluracil, an inhibitor of dihydropyrimidine dehydrogenase (DPD), developed delayed onset symptoms of unsteady gait and reduced sensation in the legs. Magnetic resonance imaging scans of the brain and neurologic examination did not support a CNS basis for the condition. Electromyograms and nerve conduction studies revealed sensorimotor polyneuropathy. Other common etiologies of peripheral neuropathy were excluded. The neurological condition of these patients stabilized after 5-FU dose reduction and partial resolution gradually occurred when protocol therapy was stopped. Although CNS symptoms may rarely complicate 5-FU therapy, peripheral neuropathy is unexpected. Patients with DPD deficiency treated with conventional doses of 5-FU typically develop acute CNS toxicity shortly after therapy, accompanied by extremely high systemic exposure to 5-FU. Patients with normal 5-FU clearance may also experience CNS toxicity, particularly with high-dose schedules, and both parent drug and its catabolites may be contributory. Since DPD was profoundly inhibited during eniluracil therapy in these two patients, it is likely that 5-FU or its active metabolites were contributing factors to the peripheral neuropathy.

Original languageEnglish (US)
Pages (from-to)525-531
Number of pages7
JournalAnti-Cancer Drugs
Volume12
Issue number6
DOIs
StatePublished - Aug 9 2001

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Leucovorin
Peripheral Nervous System Diseases
Fluorouracil
Dihydrouracil Dehydrogenase (NADP)
Dihydropyrimidine Dehydrogenase Deficiency
Neurologic Gait Disorders
Therapeutics
eniluracil
Hypesthesia
Polyneuropathies
Neural Conduction
Neurologic Examination
Electromyography
Leg
Appointments and Schedules
Parents
Magnetic Resonance Imaging
Drug Therapy
Brain

Keywords

  • Dihydropyrimidine dehydrogenase
  • Eniluracil
  • Fluorouracil
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

Cite this

Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and eniluracil. / Saif, M. Wasif; Wilson, Richard H.; Harold, Nancy; Keith, Bruce; Dougherty, David S.; Grem, Jean L.

In: Anti-Cancer Drugs, Vol. 12, No. 6, 09.08.2001, p. 525-531.

Research output: Contribution to journalArticle

Saif, M. Wasif ; Wilson, Richard H. ; Harold, Nancy ; Keith, Bruce ; Dougherty, David S. ; Grem, Jean L. / Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and eniluracil. In: Anti-Cancer Drugs. 2001 ; Vol. 12, No. 6. pp. 525-531.
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