Maximum Tolerated Dose Versus Metronomic Scheduling in the Treatment of Metastatic Cancers

This paper was posted to the arxiv along with another paper, titled

Quantitative Analysis of the Tumor/Metastasis 

System and its Optimal Therapeutic Control

The authors are clearly interested in the implications of optimal control in the metastatic setting. The paper below leaves me wondering from an evolutionary selection point of view, if metronomic therapy is actually increasing the probability of metastasis.

Maximum Tolerated Dose Versus Metronomic Scheduling in the Treatment of Metastatic Cancers

Authors

Sébastien Benzekry, Philip Hahnfeldt

Abstract

Although optimal control theory has been used for the theoretical study of anticancerous 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.

Link to the arxiv