Julie Janssen

Special patient populations such as children and pregnant women suffering from cancer represent a particular unmet clinical need, as these patient populations are not regularly included in drug development programs. In both children and pregnant women, the effects of anticancer drugs may be altered as a result of changing physiology. Changes in total body weight, total body water, and proportion of body fat may influence drug distribution, while altered organ blood flow and metabolic enzyme activity can result in changed clearance. These factors underline the importance of precision dosing in the era of precision medicine.

This thesis describes the application of PK/PD modelling and simulation to precision dosing in order to optimize anticancer treatment, with an emphasis on special patient populations. The work focuses on identifying the relationships between dose, drug exposure, and response over time. By defining variability between patients through individual characteristics such as age and body weight, individual dosing regimens can be developed to reduce variability in response.

The research includes practical recommendations for pharmacokinetic targets in pediatric oncology and the evaluation of trial designs for dose-finding in children. It also reports on the population pharmacokinetics of cytotoxic drugs in pregnant women and explores exposure-response relationships for drugs like docetaxel and capecitabine. Furthermore, the thesis addresses the application of therapeutic drug monitoring (TDM) and the development of bioanalytical methods to quantify oral anticancer drugs in human plasma. The ultimate goal of this treatment individualization is to improve treatment by increasing efficacy while protecting patients from toxicity.