The concept of time in delivering a medication: the case of anticancer agents

The duration and the doses of a drug treatment define the dose-intensity of a medication. The narrow therapeutic index of many anticancer drugs requir es a careful determination of each of the parameters that define their dose -intensity. For most anticancer drugs, the maximum tolerated dose (i.e. pot entially toxic dose) is very close to the therapeutic dose. Therefore, the frequency and the duration of drug exposure are critical time-related param eters for efficacy and toxicity. A number of clinical trials have demonstra ted the importance of the treatment schedule. Plasma pharmacokinetics has a lso been used to predict and optimize the efficacy of drugs while minimizin g their toxicity. More recently, pharmacodynamic studies have attempted to precisely evaluate the dose received at the tumor site. Finally, new imagin g techniques allow the investigation and followup of the intracellular effe cts of a drug treatment. In this paper, we review the time-related paramete rs of anticancer drugs.