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.