Pharmacodynamics of high-dose chemotherapy

There is usually considerable variability in anticancer drug plasma levels when delivered at high doses requiringstem-cell support. Given their narrow therapeuticwindows and wide interpatient pharmacokinetic variability, drug monitoring and pharmacokinetic-directed dosing representan attractive strategy in this setting. A major previous requirement to successful application of therapeuticdrug monitoringis identificationof a significant and clinically meaningful pharmacodynamic correlation between a pharmacokinetic parameter and a toxic or therapeutic outcome, or preferably, both. In this review, we will analyze the current knowledge of identified pharmacodynamic correlations in high-dose chemotherapy. We will summarize the observations from other authors and our own, on drugs employed at high doses, such as cyclophosphamide, melphalan, busulfan, carmustine, paclitaxel, or docetaxel.