[Therapeutic drug monitoring of 5-fluorouracil after its administration in high-dose protocols]. / Niveau de preuve du suivi thérapeutique pharmacologique du 5-fluorouracile au décours de son administration dans le traitement des cancers des voies aérodigestives supérieures et du cancer colorectal.

ABSTRACT

Therapeutic drug monitoring is currently investigated in patients receiving the drug by prolonged continuous infusion, either alone or associated with other chemotherapy agents. This arises from an increasing body of evidence that relates plasma fluorouracil concentrations to toxicity or effectiveness. Literature data indicate that threshold levels of exposure, as assessed by the area under the concentration-time curve, are associated with an increased risk of toxicity in patients treated for either a colorectal or a head and neck cancer. Kinetically guided dose adjustment may thus be proposed for the ongoing or the next cycle of chemotherapy. Historical comparisons and the results of a phase III multicenter randomized study in patients with metastatic colorectal cancer showed that dose-adapted fluorouracil resulted in significantly improved objective response rate, a trend to higher survival rate and fewer grade III-IV toxicities. Real-time fluorouracil monitoring may also help identifying patients with higher than expected exposure, thus providing a basis for intensifying supportive care in these patients.