In Silico Investigations of Adaptive Therapy Using a Single Cytotoxic or a Single Cytostatic Drug

Abstract

Adaptive therapy, as per the dose modulation, dose-skipping, or intermittent treatment protocol works well for treatment using a single cytotoxic drug, under a wide range of scenarios and parameter settings. In contrast, adaptive therapy works well only under a limited number of scenarios and parameter settings when using a single cytostatic drug. In general, adaptive therapy works best under conditions of higher fitness cost, higher replacement rate, higher turnover. Adaptive therapy works best when drug dosages are changed as soon as a change in tumor burden is detected. In general, it is better to pause treatment sooner than later, when the tumor is shrinking If the amount of drug used is too low, it is unable to control the sensitive cells and the tumor grows. However, if the drug dose is too high, it quickly selects for resistant cells and eventually the tumor grows out of control. However, there appears to be intermediate levels of dosing, which we call the minimum effective dose, which is able to control the sensitive cells but is not high enough to select for the resistant cells to grow out of control.