Pharmacokinetic Parameters: Potential for and Problems with Their Use As Predictors of Response to Cancer Chemotherapeutic Agents

The value of pharmacokinetic parameters of antitumor agents to predict for response to chemotherapy of patients with cancer is unknown. Factors which would lead to an expectuation that they would be of value in this regard are the requirement that cells be exposed to a minimum concentration of drug for a minimum period of time to produce cell kill and with certain agents the further requirement that this exposure be during a specific critical phase of the cell cycle. The potential limitations of these parameters for response prediction include the fact that they are whole body parameters which do not distinguish between targets for drug response and targets for dose limiting drug toxicity and that the way drugs are usually given clinically is such as to minimize the effect of patient variation in these parameters. Some practical limitations of their use are the need for very sensitive assays for their accurate definition, the need for computer analysis and the dependence of parameter estimates on the use of the correct model. It is concluded that by themselves pharmacokinetic parameters are unlikely to be of predictive value when drugs are used optimally in a clinical setting, but when considered with biochemical and other parameters may contribute to overall response prediction.