Tackling the Problems of Tumour Chemotherapy by Optimal Drug Scheduling

摘要

>Introduction: There are various strategies for overcoming the major pitfalls of cancer chemotherapy, such as toxicity and drug resistance. The scientific computing of drug scheduling by optimisation before drug administration is one among them. In a majority of these strategies, the pharmacodynamic variations are given more importance than the pharmacokinetic variations. This study was meant to analyse the importance of the pharmacokinetic parameters (φ) of the individual patients in cancer chemotherapy scheduling, along with the pharmacodynamic factors.>Methods: A mathematical model is developed and it is implemented in the open source OCTAVE GNU LINUX. Optimisation is done by using an optimization tool in OCTAVE. The present study was aimed at evaluating the daily drug dosaging and cyclic chemotherapy which are commonly practised in the chemotherapy scheduling. Four cases were analyzed with and without considering the pharmacokinetic parameters. The optimal therapy was meant to reduce the number of cancer cells to a minimum at the end of the therapy and to minimise the emergence of resistant cancer cells. Since the dose was within tolerable limits, the toxic effects could also be minimised.>Results: Even with the consideration of a 1 per cent effect (φ), the maximum possible dose and the performance index were increased in the daily scheduling. But in the cyclic therapy, even though the maximum tolerated dose or the performance index was not altered, the cumulative toxicity was greatly reduced.>Conclusion: Daily scheduling and cyclic chemotherapy can be applied alternatively more effectively, by considering the interindividual variations in the pharmacokinetic effect (φ).