Mathematical modelling for the assessment of the effect of drug application delays in metronomic chemotherapy of cancer due to physiological constraints

Several anti-angiogenic drugs in metronomic chemotherapy (MCT) scheduling in cancer have the potentiality to kill cancer cells. Theoretical analysis and experimental models have substantially indicated this potentiality. Therefore MCT may provide an option to improve the quality of life (QoL) with a quite reduced level of toxicity in the patient concerned. However, the criticism regarding MCT is that this may have a different toxicity profiling. This may require frequent interventions in the long drawn-out treatment schedule. Hence, it is worthwhile to devise a reliable estimation technique. Mathematical modelling and computer simulation techniques can assist in this regard. This, in turn, may help in the drug application decision. It is particularly important in situations where a fluctuating clearance rate of the applied drug is present. So, from dynamical perspectives, the frequencies and timings of drug stoppages need to be determined appropriately for maintaining the stability of the system without overburdening the toxicity level. Present work addresses the issue of subsequent drug administration delays and arrives at bounds of system performance and explores the treatment response in presence of physiological constraints.