ABSTRACT
Despite its limited activity as a single agent, especially when given as an intravenous bolus, 5-fluorouracil (5-FU) remains the chemotherapeutic agent of choice for advanced colorectal cancer. To enhance the efficacy of 5-FU, the optimal dose, schedule, method of administration, and biochemical modulation of 5-FU all continue to be investigated in clinical trials. 5-FU has a short plasma half-life of approximately 8-14 minutes.1 The drug is cytotoxic mainly to cells in the S phase. Therefore, with bolus administration of 5-FU, only a small proportion of cells are susceptible, as compared with administration by continuous infusion of 5-FU. Plasma levels above a threshold of 1 µM are considered necessary for the cytotoxic effect, and are thus maintained for only a few hours. 5-FU clearance is faster for schedules with continuous infusion as compared with bolus administration.2,3 The longer the infusion period of 5-FU, the lower is the tolerable dose of 5-FU. When 300 mg/m2 5-FU are administered over several weeks, plasma steady-state concentrations of less than 1 µM are measured.4 If infused over 4-5 days at a dose of 1 g/m2, plasma steady-state concentrations are in the range of 1-3 µM.5 With the use of weekly 24-hour continuous infusion with a dose of 2000-2600 mg/m2, the plasma steady-state concentration is 6-8 µM.5
