Gestion des toxicités précoces sévères au 5-fluorouracile : point sur le uridine triacetate (Vistogard®)

Abstract

For the last 60 years, 5-Fluoro-Uracil (5-FU) ranks among the most widely prescribed anticancer agents worldwide. Standard dosing with 5-FU usually claims 15–40% of severe toxicities, mostly digestive or hematologic disorders. A total of 0.5–3% of toxic deaths are regularly reported. DPD deficiency is often at the origin of the most severe side-effects. Capecitabine is an oral prodrug with the same safety profile. It was involved in suicide attempt or accidental administration to children. Uridine triacetate (Vistogard®) is indicated for the emergency treatment of adult and pediatric patients following an overdose of 5-FU or capecitabine regardless of the presence of symptoms, or who exhibit early onset, severe or life-threatening toxicity and/or early onset, unusually severe adverse reactions. Treatment must be given within 96hours following the end of 5-FU or capecitabine administration. Survival of patients with 5-FU overdose is improved from 16 to 96%. In France, Vistogard® can be obtained using Temporary Use Authorisation and 12 patients have been administered with uridine triacetate between 2013 and 2015. Hospital pharmacist plays a key role in rescuing patients with 5-FU overdose because the antidote should be administered in the 96hours following the end of the administration and the treatment shipping and delivery in France takes an average 36hours.