Clinical pharmacokinetics and pharmacodynamics of anticancer agents in pediatric patients (review)

The pharmacokinetics of several important anticancer agents used in pediatric oncology are reviewed. Many of the anticancer agents described showed age-dependent pharmacokinetics, the disposition in children being different compared to the adult pharmacokinetics. These age-dependent pharmacokinetics imply that it is inappropriate to extrapolate pharmacokinetic data from studies in adult patients. Interpatient pharmacokinetic variability in pediatric patients was large, and of a greater magnitude compared to the variability observed in adult patients. This variability in pharmacokinetics resulted in similar large variability in systemic exposure after administration of standardized doses (e.g. the maximum tolerated dose) of these anticancer agents. The variability of some of these agents is correlated with their clinical effects (either tumor response or toxicity). It is possible, using these anticancer agents, to monitor pediatric patients, identifying those patients at risk of severe toxicity (high systemic exposure) or those patients who may not benefit from treatment (Low systemic exposure). These pharmacodynamic relationships are described in this paper, since such correlations may contribute to further optimization of chemotherapy in pediatric patients.