Low-intensity combination chemotherapy maximizes host survival time for tumors containing drug-resistant cells (Q1196633)

The authors pose the following question. Given a tumor of size \(N(t)\) and two therapeutical agents \(A\) and \(B\), such that parts of the tumor can develop a resistance against \(A\) or \(B\) or both. What is the best application scheme to maximize the survival time defined by \(\sup\{t;N(t)<N_{\max}\}\)? After describing the system by a system of ordinary differential equations with interaction terms the authors reduce the question in several steps to a sequence of discrete problems that can be tackled by nonlinear optimization techniques developed by one of the authors. It turns out that high doses are not optimal and that it is better to keep the size of the tumor constant on a high level.