5-FLUOROURACIL CARDIOTOXICITY - A QUESTIO N OF FORMULATION

The cardiotoxicity of 5-fluorouracil (FU) was attributed to degradatio n compounds present in the injected vials, fluoroacetaldehyde (Facet)a nd fluoromalonaldehydic acid (FMald). These compounds are formed with time and the basic medium necessary to solubilize FU. FU-NaOH vials we re much less cardiotoxic than FU-Tris vials on the isolated perfused r abbit heart model since, in FU-Tris vials, Facet and FMald are stored in stable ''depot'' forms, which are adducts with Tris, whereas, in FU -NaOH vials, they are extensively chemically transformed. Cardiotoxic fluoroacetate (FAG), arising from Facet metabolization, was found in u rine of patients, with a ratio FAC/FU catabolites 10-30 fold lower in patients treated with FU-NaOH than in those treated with FU-Tris.