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Evolutionary Based Adaptive Dosing Algorithms: Beware the Cost of Cumulative Risk

H. Mistry

Published 2020 in bioRxiv

ABSTRACT

Application of theories from ecology to cancer is growing. One such idea involves using drug sensitive cells to control drug resistant cells by cycling treatment on and off based on a marker of tumour burden. Many literature studies have highlighted the benefit of this approach when using time till reaching a certain level of burden as an end-point. These studies though have not considered that patients need to survive up until a certain time-point with a higher level of tumour burden compared to standard dosing to gain this benefit. Within this study once this cumulative cost is accounted for it can be seen that adaptive dosing, counter-intuitively, is likely to lead to poorer prognosis than continuous dosing. This study highlights that evolutionary based adaptive dosing algorithms may not be the “parachute” its protagonists believe it to be.

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