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J Theor Biol. 2013 Oct 21;335:235-44. doi: 10.1016/j.jtbi.2013.06.036. Epub 2013 Jul 11.

Maximum tolerated dose versus metronomic scheduling in the treatment of metastatic cancers.

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Center of Cancer Systems Biology, Steward Research & Specialty Projects Corp., St Elizabeth's Medical Center, Tufts University School of Medicine, Boston 02135, USA.


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.


Cancer modeling; Metastasis; Metronomics; Scheduling optimization

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