Clinical pharmacokinetic study of 5-FU in continuous 5-day infusions for head and neck cancer.
Twenty-nine previously untreated patients with head and neck carcinoma received a total of 63 cycles of an initial chemotherapy protocol combining cis-platinum (100 mg/m2 on day 1) and continuous 5-day infusion of 5-FU (1000 mg/m2/24 h) from day 2 to day 6. This protocol was repeated on day 16 and day 31. Two daily blood samples obtained from all patients every day during 5-FU administration were analyzed by HPLC to determine the 5-FU concentrations. In the majority of cases a constant elevation was observed in total 5-FU cycle exposure (C X T) from cycle to cycle. A close relationship was demonstrated between elevated 5-FU C X T values (over 30 000 ng h ml-1) and the frequency of cycles in which signs of toxicity (myelosuppression, mucositis, diarrhea) were observed. By contrast, no obvious association was noted between response to treatment and systemic 5-FU exposure.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D002945:Cisplatin; D005472:Fluorouracil