The tris formulation of Fluorouracil is more cardiotoxic than the sodium-salt formulations.

The cardiotoxicity of 5-fluorouracil (FU) was attributed to degradation compounds present in the injected vials, fluoroacetaldehyde (Facet) and fluoromalonaldehydic acid (FMald). FU-NaOH vials were much less cardiotoxic than FU-Tris vials on the isolated perfused rabbit heart model since Facet and FMald are stored in stable depot forms in FU-Tris vials whereas, in FU-NaOH vials, they are extensively transformed. Cardiotoxic fluoroacetate (FAG), coming from Facet metabolization, was found in urine 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.

Multicenter phase II study of brequinar sodium in patients with advanced breast cancer.

In this study, 34 patients with advanced breast cancer were treated with brequinar sodium: 75% of the patients were postmenopausal, and 94% had received chemotherapy previously; 50% had previously received an anthracycline-containing regimen. Brequinar was administered intravenously at a median weekly dose of 1,200 mg/m2. The toxicity was moderate, with 17 patients (50%) experiencing grade 3 or 4 toxicity.