title: Early-Onset 5-Fluorouracil Toxicity in a Patient Negative for Dihydropyrimidine Dehydrogenase Mutations: The Clinical Course of Reversal with Uridine Triacetate.
abstract: An antimetabolite pyridine analog, 5-fluorouracil (5-FU), is used to treat solid tumors. Early toxicities may occur at standard doses of 5-FU due to dihydropyrimidine dehydrogenase (DPD) deficiency. Uridine triacetate, approved by the Food and Drug Administration in 2015, is an oral prodrug of uridine, a pharmacologic antidote for 5-FU toxicity. To our knowledge, this is the first case report that documents the clinical course of a patient treated with uridine triacetate to reverse early-onset 5-FU toxicity negative for DPD mutations. We describe the case of a 73-year-old man with anal cancer treated with standard-of-care chemotherapy and radiation. Two days after completion of his initial 5-FU infusion, the patient developed severe mucositis and extreme fatigue, followed by a rapid decline in his blood cell counts and fevers. The patient was initiated on uridine triacetate 86 hours after completion of his 5-FU infusion. Over a 10-day hospital length of stay, the patient's absolute neutrophil count recovered to within normal limits, and his mucositis significantly improved. At follow-up visits, the patient denied any residual symptoms of 5-FU toxicity. We describe the patient's clinical course from hospital presentation to 31 days after initiation of uridine triacetate.
authors.affiliation: Department of Pharmacy, Lahey Hospital & Medical Center, Burlington, Massachusetts.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Vaudo
authors.affiliation: Department of Pharmacy, Lahey Hospital & Medical Center, Burlington, Massachusetts.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gil
authors.affiliation: Department of Hematology/Oncology, Lahey Hospital & Medical Center, Burlington, Massachusetts.
authors.forename: Kari
authors.initials: K
authors.lastname: Galuski
authors.affiliation: Department of Hematology/Oncology, Lahey Hospital & Medical Center, Burlington, Massachusetts.
authors.forename: Corrine
authors.initials: C
authors.lastname: Zarwan
authors.affiliation: Department of Hematology/Oncology, Lahey Hospital & Medical Center, Burlington, Massachusetts.
authors.forename: Francis W
authors.initials: FW
authors.lastname: Nugent
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000368:Aged; D000931:Antidotes / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005221:Fatigue / Q000139:chemically induced; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism; D013997:Time Factors; D014529:Uridine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000085:Acetates; D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; C000609666:uridine triacetate; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil; D014529:Uridine
keywords: 5-fluorouracil; adverse drug reaction; early-onset toxicity; uridine triacetate