Intermediate dose 5-fluorouracil-induced encephalopathy

Jpn J Clin Oncol. 2006 Jan;36(1):55-9. doi: 10.1093/jjco/hyi214. Epub 2006 Jan 25.


As an acute neurotoxicity, high dose 5-fluorouracil (5-FU)-induced encephalopathy is well-known, but encephalopathy associated with lower dose is rarely reported. Here, we report a case of a male with anal cancer who was treated with 5-FU 1000 mg/m(2), continuous infusion for 5 days q4 weeks. At the second and the fourth cycles of chemotherapy, sudden confusion, cognitive dysfunction and disorientation occurred during 5-FU infusion. They were accompanied by hyperammonemia in the absence of focal neurological deficits or structural abnormalities. These symptoms completely disappeared and the serum ammonia level returned to normal after discontinuation of 5-FU and conservative care. In order to investigate a possible deficit of dihydropyrimidine dehydrogenase (DPD), we checked its mRNA level before and after treatment using real-time PCR. The patient's pre-treatment level was 80% compared with reference group, and it was elevated up to 187% of initial after 5-FU treatment, implying that that his encephalopathy may be 5-FU catabolite type rather than DPD deficiency. In conclusion, we report that encephalopathy can develop even with the dose of 5-FU lower than ever reported, and it should be considered as a differential diagnosis for proper management.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Anus Neoplasms / drug therapy
  • Anus Neoplasms / pathology
  • Cisplatin / administration & dosage
  • Diagnosis, Differential
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fluorouracil / adverse effects*
  • Humans
  • Hyperammonemia / complications
  • Infusions, Intravenous
  • Male
  • Neoplasm Invasiveness
  • Neurotoxicity Syndromes / diagnosis
  • Neurotoxicity Syndromes / etiology*


  • Antimetabolites, Antineoplastic
  • Cisplatin
  • Fluorouracil