PLASMA 5-FLUOROURACIL AND ALPHA-FLUORO-BETA-ALANIN ACCUMULATION IN LUNG-CANCER PATIENTS TREATED WITH CONTINUOUS-INFUSION OF CISPLATIN AND 5-FLUOROURACIL

This study was undertaken to investigate the day-to-day pharmacokineti c variability of 5-fluorouracil (5FU) given as a continuous i.v. infus ion concomitantly with cisplatin. Ten lung cancer patients were invest igated during the first course of chemotherapy. All patients had advan ced, previously untreated, inoperable non-small-cell lung cancer. They received continuous infusions of cisplatin given at 100 mg/m(2) over 5 days and of 5FU given at 1 g/m(2) daily from day 2 to day 5. Both dr ugs were infused i.v. for 24 h/day at a constant rate with a volumetri c pump. Blood samples were drawn from day 2 to day 5, every 4 h from 8 a.m. to 8 p.m. and every 2 h during the night (8 p. m. to 8 a.m.). Pl asma 5FU and FBAL concentrations were determined simultaneously by gas chromatography-mass spectrometry. Plasma 5FU concentrations varied wi dely over the 4-day treatment course for each patient. Despite continu ous constant-rate 5FU administration, plasma 5FU concentrations were s ignificantly lower between 8 a. m. and 8 p.m. than during the night. M ean plasma concentrations of 5FU and FBAL increased significantly from the 1st day (0.42 and 1.19 mu g/ml for 5FU and FBAL, respectively) to the 4th day of 5FU infusion (0.67 and 1.78 mu g/ml for 5FU and FBAL, respectively). Further study is warranted to elucidate the mechanisms of the observed increase in plasma 5FU concentrations as well as its r elationship with cisplatin coadministration and to assess the clinical relevance of this plasma 5FU accumulation.