Nonlinear model predictive control for dosing daily anticancer agents using a novel saturating-rate cell-cycle model

Abstract

A nonlinear model predictive control (NMPC) algorithm was developed to dose the chemotherapeutic agent tamoxifen based on a novel saturating-rate, cell-cycle model (SCM). Using daily tumor measurements, the algorithm decreased tumor volume along a specified reference trajectory in simulated animals over 4 months. In mismatch case studies, controllers based on the Gompertz model (GM) yielded equivalent total drug delivered and elapsed time to t 99 % reference step convergence to those obtained using the SCM, though this performance was dependent on the cell-cycle phase of drug effect. Overall, the NMPC algorithm is suitable for dosing chemotherapeutics with regular administration schedules and may be adapted for regularly administered chemotherapeutics other than tamoxifen.