TO WHICH CRITERION SHOULD THE DOSE OF ANTICANCER DRUG BE ADAPTED

The dose of anticancer drugs is currently adjusted to the body surface area of the patient, although for a given body surface, patients have different distribution and metabolism for a given drug. The dose adju stment to the tumour drug content was studied, we noted that it is not always possible to obtain a tumour sample; the sample and its drug co ntent may not be representative of the whole tumour content, this meas ured drug content is neither indicative for the evaluation of the dose to be administered, nor indicative of the chemotherapy efficacy. The best criterion for the dose adjustment seems to be the plasma concentr ation of the drug. Correlations between drug plasma concentration and clinical data are examined. The relationship between plasma concentrat ion and efficacy cannot be excellent, since it depends on the presence of resistant cells and on the blood flow through the tumour. A relati onship between plasma concentration and toxicity has been reported wit h many anticancer drugs. The drug plasma concentration and the area un der the curve (AUC) give better correlations than the administered dos e with efficacy and toxicity. Different methods of dose adjustment are reported. They use mathematical models which allow to decrease the nu mber of blood samples, without losing precision in the pharmacokinetic parameter evaluation. In conclusion, the dose adjustment to the drug plasma concentration or to the AUC can play an important role in impro ving the chemotherapy efficacy, while toxicity is reduced.