[Pharmacokinetic monitoring with dosage adjustment of 5 fluorouracil administered 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 patients revealed that both the time-concentration product (ASC) for the entire 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 (97 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 haematological and/or digestive tract toxicity (47 to 33%). Moreover, although dose reduction was often performed, the clinical response was not affected (42-44%), neither was the median survival time (8.8 months-14.1 months in control and adapted groups respectively).
Wihlm
J
J
Centre régional de lutte contre le cancer Paul-Strauss, Strasbourg, France.
Levêque
D
D
Velten
M
M
Klein
T
T
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D002945:Cisplatin; D005472:Fluorouracil
Surveillance pharmacocinétique avec adaptation de posologie du 5-fluorouracile administré en perfusion continue.