Clinical experience with uridine triacetate for 5-FU overexposure: An update.

Abstract

e20592 Background: 5-Fluorouracil (5-FU) is broadly used to treat solid tumors. It is typically administered by IV infusion, at or near its maximum tolerated dose, over several days. The use of infusion pumps increases the possibility of life-threatening or lethal toxicity due to errors in pump programming, infusion reservoir errors and dosage miscalculations. Partial or total dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients (up to 3% of the population) to impaired 5-FU elimination, can also result in serious or lethal toxicity, Uridine triacetate is an orally bioavailable direct biochemical antagonist of 5-FU toxicity that has been used successfully to treat patients in emergency overdose situations as well as patients with known or suspected overexposure to 5-FU due to DPD deficiency or other causes. Approximately 100 patients at excess risk of 5-FU toxicity due to 5-FU overdose, accidental Xeloda (capecitabine) ingestion, or possible DPD deficiency (rapid onset of severe toxicities) have been treated with uridine triacetate using a common treatment regimen and protocol. More than 80 of these cases have occurred since uridine triacetate data were presented at ASCO in 2009. Methods: Uridine triacetate was provided under emergency IND provisions or an expanded access protocol when requested by qualified clinical sites following 5-FU overexposures, most due to infusion pump errors. Patients received uridine triacetate (10g q6h for 20 doses) as soon as possible after recognition of the overdose or possible clearance defect. Clinical outcomes, including safety and resumption of chemotherapy, were monitored. Results: To date, 98 patients overexposed to 5-FU have been treated with uridine triacetate. 96 of these 98 patients recovered fully. Reductions in or absence of GI, hematologic, and other toxicities associated with 5-FU poisoning were observed. Adverse events attributable to urdine triacetate were infrequent and mild in severity. Conclusions: Uridine triacetate appears to be a safe and effective life-saving antidote for 5-FU overexposure in emergency situations.