Reversal of 5-fluorouracil-induced toxicity by oral administration of uridine

Background: Previous preclinical and clinical investigations have shown that the combined administration of 5-fluoro-uracil (5-FU) with delayed uridine can reverse side effects induced by 5-FU. This biochemical modulation-based combination may increase the therapeutic index of 5-FU. Patients and methods: Seven patients with advanced cancer were treated weekly with 5-FU at increasing dosages starting at a dose of 600 mg/m². Five patients developed dose-limiting leukopenia, and two patients developed thrombocytopenia. At the dose-limiting toxicity level, 5-FU treatment was repeated and followed after 3 hours by oral uridine (5 g/m² q 6 hr) during 72 hours. Results: 5-FU-induced leukopenia was reversed for several weeks after the administration of oral uridine. However, thrombocytopenia was not reversed. Side effects of the combined treatment consisted of mild diarrhea in five of the seven patients. Conclusions: These data indicate that oral uridine can reduce the severity of 5-FU-induced myelosuppression.