A mathematical justification for metronomic chemotherapy in oncology

We mathematically justify metronomic chemotherapy as the best strategy to apply many cytotoxic drugs in oncology for both curative and palliative approaches, assuming the classical pharmacokinetic model together with the Emax pharmacodynamic and the Norton-Simon hypothesis. From the mathematical point of view, we will consider two mixed-integer nonlinear optimization problems, where the unknowns are the number of the doses and the quantity of each one, adjusting the administration times a posteriori