THERAPEUTIC DRUG-MONITORING WITH DOSE ADJUSTMENT OF 5-FU ADMINISTRATED BY CONTINUOUS-INFUSION

Therapeutic drug monitoring of 5-FU was investigated in patients with head and neck cancer treated with cisplatin (100 mg/m2) followed by 5- day continuous infusion of 5-FU (1 g/m2/d). In a first step, the 5-FU pharmacokinetic and pharmacodynamic analysis of 25 cycles for 14 patie nts revealed that both the time-concentration product (ASC) for the en tire cycle and the half-cycle were predictive of cycle toxicity and a dose adjustment diagram was established. In a second experiment, this diagram was used for treatment monitoring in a group of 35 patients (9 7 cycles). The clinical toxicity and response were compared with those of a retrospective group of 55 patients (184 cycles) treated with the same protocol without dose adjustment. Pharmacokinetic follow-up of 5 -FU has proved to be an objective means to significantly reduce haemat ological and/or digestive tract toxicity (47 to 33%). Moreover, althou gh dose reduction was often performed, the clinical response was not a ffected (42-44%), neither was the median survival time (8.8 months-14. 1 months in control and adapted groups respectively).