CAN PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES IMPROVE CANCER-CHEMOTHERAPY

Background: The exploitation of pharmacokinetic-pharmacodynamic relationships is worthwhile for drugs where there is difficulty or delay in obtaining clinical evidence of therapeutic or toxic effects, where there is a clear relationship between the pharmacokinetics and pharmacodynamics, and where the drug has a small therapeutic index. These criteria are amply met by cytotoxic anticancer agents. In particular, an extensive literature for all classes of cancer chemotherapeutics shows that the correlation between pharmacokinetic parameters (peak concentration, area under the plasma concentration-time curve, clearance or steady-state levels) and toxicity is in many cases better than the relationship between dose and toxicity. Adaptive dosing: Prospective studies of dose adaptation on the basis of pharmacokinetic or pharmacodynamic information, with or without feedback control, have shown that pharmacologically guided dosing is feasible. Adaptive dosing results in reduced pharmacokinetic variability and more consistent toxicity. Currently, there are insufficient prospective studies to allow conclusions concerning the efficacy of such a dosing system.