Pharmacokinetic principles of locoregional chemotherapy.

The rationale for regional chemotherapy is based on the premise that certain tumours are confined to compartments within the body for a large part of their natural history and that the dose-response curves for most cytotoxic drugs are steep. If the drug can be introduced locally, then much higher drug concentrations can be achieved at the site of bulk tumour and the prospects of drug induced cytotoxicity enhanced. The general pharmacokinetic principle guiding regional chemotherapy is that the rate of drug clearance from the local compartment (peritoneal and pleural cavities, vascular territories) is smaller than total body clearance, creating a concentration differential in favour of the local compartment harbouring the majority of the cancer. There is good evidence, under certain situations, that pharmacokinetic advantage can translate to clinical advantage.