5-Fluorouracil Neurotoxicity in a Patient With Normal Dihydropyrimidine Dehydrogenase Activity

Abstract

5-fluorouracil (5-FU) is a well-known chemotherapeutic agent used for the treatment of colon cancer and other solid malignancies. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catalyzes 5-FU, and if a patient is deficient, such as through a gene mutation, they can be predisposed to severe toxicity. Although 5-FU-induced neurotoxicity is extremely rare, it can be fatal. We report a case of 5-FU neurotoxicity in a 56-year-old male patient with keratinizing squamous cell carcinoma of the anal canal on concurrent chemoradiation therapy consisting of 5-FU, mitomycin, and radiotherapy. Encephalopathy, dysarthria, and ataxia were noted on day three of treatment. MRI of the brain showed a pattern of global anoxic brain injury. DPD testing was negative for polymorphism, and the patient's symptoms improved after treatment with uridine triacetate, the treatment for 5-FU toxicity.

Keywords: 5 fluorouracil; 5-fu neurotoxicity; 5-fu toxicity; dihydropyrimidine dehydrogenase deficiency; uridine triacetate.

Figure 1. MRI of the brain obtained three days after symptom onset revealed significant diffusion restriction along the corpus callosum, which markedly improved on repeat MRI of the brain three weeks later