A review of optimal chemotherapy protocols: From MTD towards metronomic therapy

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We review mathematical results about the qualitative structure of chemotherapy protocols that were obtained with the methods of optimal control. As increasingly more complex features are incorporated into the mathematical model - progressing from models for homogeneous, chemotherapeutically sensitive tumor cell populations to models for heterogeneous agglomerations of subpopulations of various sensitivities to models that include tumor immune-system interactions - the structures of optimal controls change from bang-bang solutions (which correspond to maximum dose rate chemotherapy with restperiods) to solutions that favor singular controls (representing reduced dose rates). Medically, this corresponds to a transition from standard MTD (maximum tolerated dose) type protocols to chemo-switch strategies towards metronomic dosing. © EDP Sciences, 2014.

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