Optimal Protocols for the Anti-VEGF Tumor Treatment

Cancer treatment using the antiangiogenic agents targets the evolution of the tumor vasculature. The aim is to significantly reduce supplies of oxygen and nutrients, and thus starve the tumor and induce its regression. In the paper we consider well established family of tumor angiogenesis models together with their recently proposed modification, that increases accuracy in the case of treatment using VEGF antibodies. We consider the optimal control problem of minimizing the tumor volume when the maximal admissible drug dose (the total amount of used drug) and the final level of vascularization are also taken into account. We investigate the solution of that problem for a fixed therapy duration. We show that the optimal strategy consists of the drug-free, full-dose and singular (with intermediate values of the control variable) intervals. Moreover, no bang-bang switch of the control is possible, that is the change from the no-dose to full-dose protocol (or in opposite direction) occurs on the interval with the singular control. For two particular models, proposed by Hahnfeldt et al. and Ergun et al., we provide additional theorems about the optimal control structure. We investigate the optimal controls numerically using the customized software written in MATLAB (R), which we make freely available for download. Utilized numerical scheme is based on the composition of the well known gradient and shooting methods.