Uridine triacetate as a life-saving antidote to capecitabine toxicity.

e21612 Background: Uridine triacetate was approved by FDA in 2015 for adult and pediatric patients who receive an overdose of 5-fluorouracil or capecitabine or who exhibit early-onset, severe or life-threatening toxicities. Early-onset toxicities from capecitabine or 5-FU treatment are due to various metabolic causes, including DPD deficiency, and can be fatal. Uridine triacetate is an oral prodrug of uridine, a direct antagonist of 5-FU, that dilutes and competes with toxic 5-FU metabolites, particularly FUTP incorporation into RNA, reducing morbidity and mortality due to 5-FU and capecitabine. Methods: Uridine triacetate has been studied in 2 trials (173 patients) to date, including 13 who received an overdose of capecitabine or developed early-onset, severe toxicities. The Sponsor (Wellstat Therapeutics) was contacted upon recognition of an overdose or early-onset toxicity and evaluated patient eligibility. Adults (n = 6 overdose and 4 early-onset) were to receive 10 g of uridine triacetate orally every 6 hr for 20 doses. Pediatric patients (n = 3) were to receive 6.2 g/m2 orally every 6 hr for 20 doses. Uridine triacetate was to start within 96 hr following the end of capecitabine. The primary endpoint was survival at 30 days following uridine triacetate. All patients were monitored for safety. Results: All 6 adult capecitabine suicidal overdose cases (up to 28,000 mg at once) and all 3 pediatric patients who accidentally took capecitabine recovered fully within 30 days post-treatment with uridine triacetate. Both patients who presented with multiple severe post-capecitabine toxicities but initiated treatment with uridine triacetate > 96 hr died. In contrast, both patients who presented with similar multiple severe early-onset toxicities but who started uridine triacetate within the recommended 96 hr post capecitabine fully recovered. Only one AE (vomiting) was attributed to uridine triacetate. Conclusions: Uridine triacetate was a safe and effective life-saving treatment for patients following potentially lethal capecitabine overexposure or early-onset toxicities when administered within 96 hr post capecitabine dosing.