Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency.
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.
Shehata
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N
Division of Medical Oncology, Newfoundland Cancer Treatment and Research Foundation, St. John's, NF, Canada.
Pater
A
A
Tang
S C
SC
D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy / Q000201:enzymology; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced*; D010088:Oxidoreductases / Q000172:deficiency*
D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil