  Although optimal control theory has been used for the theoretical study of
anti-cancerous drugs scheduling optimization, with the aim of reducing the
primary tumor volume, the effect on metastases is often ignored. Here, we use a
previously published model for metastatic development to define an optimal
control problem at the scale of the entire organism of the patient. In silico
study of the impact of different scheduling strategies for anti-angiogenic and
cytotoxic agents (either in monotherapy or in combination) is performed to
compare a low-dose, continuous, metronomic administration scheme with a more
classical maximum tolerated dose schedule. Simulation results reveal
differences between primary tumor reduction and control of metastases but
overall suggest use of the metronomic protocol.
