Toward Model-Based Chemotherapy Treatment Design

Summary

Pharmacokinetic models of anticancer compounds are growing in prevalence, and these provide implicitly useful guidance in drug dosing. With the construction of pharmacodynamic models of unperturbed, and treated, tumor growth, as well as toxicity, it becomes possible to explicitly employ PK/PD models to design cancer treatment schedules. This work has demonstrated how current modeling tools and insight can be integrated to develop mathematical descriptions of drug kinetics (PK) and effect (PD) that are quantitatively accurate while having a structure that is amenable to model-based optimization. The present study was preclinical in nature, using human tumor xenografts, and the concept is generalizable for use in human patients with a modest increase in treatment-related measurements. A long-term goal of this work is to develop inter-species scaling factors to allow preclinical results, such as those in the present study, to be generally applicable in a priori dosage design for clinical treatment. Finally, based on the premise that model quality limits achievable performance [4], the development of measurement techniques or devices to sample at finer spatial and temporal resolutions could lead to more detailed PK and PD models and hence improved dosage design algorithms.