CLINICAL PHARMACODYNAMIC-PHARMACOKINETIC RELATIONSHIPS OF CISPLATINUMAND ETOPOSIDE

Currently, the dose of anticancer drugs is adjusted according to patie nt body surface area, although the best criterion for dose adjustment seems to be the plasma concentration of the drug, since a correlation has been established between plasma concentration and efficacy for sev eral drugs. We report here similar results with etoposide and cisplati num. The plasma concentration and the area under the curve (AUC) of et oposide and platinum (Pt) were higher in responders compared to non-re sponders, and etoposide clearance was higher in responders. The etopos ide toxicity (assessed by the polymorphonuclear blood count) was highe r in responders. There was a good correlation between the Pt concentra tion and creatininaemia. The AUC for Pt was significantly higher in pa tients with nausea and vomiting. There was no correlation between the injected dose of either drug and efficacy or toxicity. It is not possi ble to assign efficacy to either compound since they were injected sim ultaneously. We conclude that when the plasma etoposide or platinum co ncentrations are low, tumour response is unlikely.