Cancer Res Treat.  2010 Jun;42(2):118-120.

A Case of 5-Fluorouracil Induced Encephalopathy

• Kwon KA
• Kwon HC
• Kim MC
• Kim SH
• Oh SY
• Lee S
• Kim HJ

Abstract

Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m2) for 5 days and cisplatin (60 mg/m2) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days.

Keyword

5-FU; Neurotoxicity; Encephalopathy

MeSH Terms

Adult
Ammonia
Brain
Chemotherapy, Adjuvant
Cisplatin
Dihydrouracil Dehydrogenase (NADP)
Enema
Female
Fluorouracil
Gastrectomy
Humans
Lactulose
Magnetic Resonance Spectroscopy
Paranoid Disorders
Retention (Psychology)
Thiamine
Ammonia
Cisplatin
Dihydrouracil Dehydrogenase (NADP)
Fluorouracil
Lactulose
Thiamine

Figure

• 

  Fig. 1 Brain MRI, the T2W image. There is no abnormal signal of the brain parenchyma.

Reference

1. Grem JL. 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs. 2000; 18:299–313. PMID: 11081567.

2. Pirzada NA, Ali II, Dafer RM. Fluorouracil-induced neurotoxicity. Ann Pharmacother. 2000; 34:35–38. PMID: 10669184.

3. Koenig H, Patel A. Biochemical basis for fluorouracil neurotoxicity. The role of Krebs cycle inhibition by fluoroacetate. Arch Neurol. 1970; 23:155–160. PMID: 5430334.

4. Kim YA, Chung HC, Choi HJ, Rha SY, Seong JS, Jeung HC. Intermediate dose 5-fluorouracil-induced encephalopathy. Jpn J Clin Oncol. 2006; 36:55–59. PMID: 16436463.

5. Heier MS, Dornish JM. Effect of the fluoropyrimidines 5-fluorouracil and doxifluridine on cellular uptake of thiamin. Anticancer Res. 1989; 9:1073–1077. PMID: 2530931.

6. Heggie GD, Sommadossi JP, Cross DS, Huster WJ, Diasio RB. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res. 1987; 47:2203–2206. PMID: 3829006.

7. Etienne MC, Lagrange JL, Dassonville O, Fleming R, Thyss A, Renee N, et al. Population study of dihydropyrimidine dehydrogenase in cancer patients. J Clin Oncol. 1994; 12:2248–2253. PMID: 7964939.

8. Yeh KH, Cheng AL. High-dose 5-fluorouracil infusional therapy is associated with hyperammonaemia, lactic acidosis and encephalopathy. Br J Cancer. 1997; 75:464–465. PMID: 9020500.

9. Cho IJ, Chang HJ, Lee KE, Won HS, Choi MY, Nam EM, et al. A case of Wernicke's encephalopathy following fluorouracil-based chemotherapy. J Korean Med Sci. 2009; 24:747–750. PMID: 19654964.

10. Cheung WY, Fralick RA, Cheng S. The confused cancer patient: a case of 5-fluorouracil-induced encephalopathy. Curr Oncol. 2008; 15:234–236. PMID: 19008998.

11. Takimoto CH, Lu ZH, Zhang R, Liang MD, Larson LV, Cantilena LR Jr, et al. Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Clin Cancer Res. 1996; 2:477–481. PMID: 9816193.

12. Baek JH, Kim JG, Kim SN, Kim DH, Sohn SK, Hong YJ, et al. Unpredicted severe toxicity after 5-fluorouracil treatment due to dihydropyrimidine dehydrogenase deficiency. Korean J Intern Med. 2006; 21:43–45. PMID: 16646564.