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 -florouracil (5-FU) in 23 patients with head and neck cancer treated w ith carboplatin (360 mgimz) followed by 5 day continuous infusion of 5 -FU (lg/m(2)/day). The pharmacokinetic profile of 5-FU was characteriz ed for 36 cycles and was compared with the patient's tolerance. Toxic cycles (greater than or equal to grade 1, WHO grading) were associated with higher values of area under the serum concentration-time curve ( AUG) than those of non toxic cycles. In addition AUC values of 37000 n g.h.ml-1 and 21000 ng.h.ml-l for the entire cycle and the half-cycle r espectively were found to be predictive of toxicity. These threshold v alues are identical to those determined in our previous study with the cisplatin - 5-FU regimen. Hence, patients treated with carboplatin an d infusional 5-FU might benefit from 5-FU blood level monitoring using the same dose adjustment