Pharmacodynamics of 5-fluorouracil combined with carboplatin in patients with head and neck cancer.
The objective of our work was to investigate the pharmacodynamics of 5-fluorouracil (5-FU) in 23 patients with head and neck cancer treated with carboplatin (360 mg/m2) followed by 5 day continuous infusion of 5-FU (lg/m2/day). The pharmacokinetic profile of 5-FU was characterized for 36 cycles and was compared with the patient's tolerance. Toxic cycles (> or = grade 1, WHO grading) were associated with higher values of area under the serum concentration-time curve (AUC) than those of non toxic cycles. In addition, AUC values of 37000 ng.h.ml-1 and 21000 ng.h.ml-1 for the entire cycle and the half-cycle respectively were found to be predictive of toxicity. These threshold values are identical to those determined in our previous study with the cisplatin-5-FU regimen. Hence, patients treated with carboplatin and infusional 5-FU might benefit from 5-FU blood level, monitoring using the same dose adjustment diagram.
Wihlm
J
J
Centre Paul Strauss, Strasbourg, France.
Leveque
D
D
Klein
T
T
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000009:adverse effects / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged
D016190:Carboplatin; D005472:Fluorouracil