ABSTRACT
Daily 24-hour serum levels of ftorafur (FT), 5-FU, and a major FT metabolite, dehydroftorafur (DFT), were monitored by high-performance liquid chromatography as part of a phase I study designed to evaluate FT as a radiosensitizing 5-FU pro-drug in patients with advanced gastrointestinal cancers. At a daily iv bolus FT dose of 1.0 g/m2, 5-FU was not detected in serum concentrations above the reliable assay limits of approximately 25 ng/ml; FT did not generate the extracellular (serum) 5-FU concentrations required for sensitization by 5-FU per se. DFT was present in every patient serum tested and was confirmed to be a metabolite of FT by in vitro conversion to 5-FU. Chemical ionization solid-probe mass spectrometry of the DFT metabolite indicates the dehydro FT structure proposed by other researchers. In six of eight patients monitored, a consistent relationship was noted between serum levels of FT and DFT.
