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

TL;DR

This study uses a mathematical model to compare the effects of maximum tolerated dose and metronomic scheduling of cancer treatments on primary tumors and metastases, highlighting the potential benefits of continuous low-dose therapy.

Contribution

It introduces an organism-scale optimal control model for metastatic cancer treatment, comparing scheduling strategies and emphasizing the advantages of metronomic therapy.

Findings

Metronomic scheduling better controls metastases than MTD.

Simulation shows differences in primary tumor reduction versus metastasis control.

Metronomic protocol generally recommended based on simulation results.

Abstract

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.