The safety of uridine triacetate was assessed in 173 patients in 2 compassionate use, single arm, open-label, multicentre trials. Adult and paediatric patients presenting with fluorouracil or capecitabine overdose and/or a rapid early onset of severe fluorouracil or capecitabine toxicity were enrolled into the study. Patients received emergency treatment with uridine triacetate at a dose of 10 grams (or 6.2 g/m2 for paediatric patients, maximum 10 grams per dose) orally every 6 hours for a total of 20 doses, commencing as soon as possible after fluorouracil or capecitabine and the recognition of the need for antidotal treatment. The primary efficacy endpoint was patient survival or the resumption of chemotherapy during the 30 day monitoring period.r
Prior to uridine triacetate, the standard treatment for a 5-FU overdose was supportive care, including antiemetics, intravenous fluids, antibiotics, intensive care, and medications to treat myelosuppression. Therefore, in these studies, the overall efficacy of treatment with uridine triacetate was compared with a historical cohort of cases in which patients with a documented 5-FU overdose received best supportive care.r
Of the 173 patients included in the study, 147 were treated with uridine triacetate following an overdose of fluorouracil or capecitabine and 26 patients were treated after exhibiting early-onset, severe, or life-threatening toxicities. Six out of the 173 patients were paediatric cases.r
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Of the 173 patients treated with uridine triacetate, 158 patients (94%) survived to day 30 and 56 out of 173 patients had resumed chemotherapy prior to day 30.
There were 147 patients with a fluoropyrimidine overdose included in the study. 5 patients were lost to follow up, leaving 142 evaluable patients, of which 137 (96%) survived to day 30.
In contrast, mortality was 84% (21 of 25 patients) in a historical cohort of patients who did not receive uridine triacetate.r
Treatment with uridine triacetate was commenced within the first 96 hours for 18 out of the 26 patients presenting with early-onset severe toxicity and all 18 patients survived and recovered.
Of the 8 patients who initiated treatment beyond 96 hours, 3 patients survived and 5 patients died. The deaths were attributed to sequelae of fluorouracil toxicities.r
In the study there was a high rate of treatment compliance, with a median number of 20 doses taken per subject (range 3-23).
Overall, uridine triacetate is well tolerated by most patients. Mild to moderate nausea, vomiting and diarrhoea have been reported. rr