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Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer

Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer

Benjamin K Schneider

Iowa State University

21 November 2019

Bevacizumab-pemetrexed/cisplatin combination therapy (BEV-PEM/CIS) is a first line therapeutic for non-small cell lung cancer (NSCLC). BEV-PEM/CIS has a narrow therapeutic window - the range of dosages which both reduce the size and spread of the cancer and do not lead to overdose or a damaging accumulation of side-effects. Those side-effects include damage to rapidly dividing healthy cells such as bone marrow and blood cell progenitors. For this reason, BEV-PEM/CIS dosages cannot be scaled to treat aggressive NSCLC. Recent literature suggests that administering bevacizumab and pemetrexed/cisplatin sequentially, rather than concurrently, would greatly improve the efficacy of the combination therapy without leading to additional side-effects. Unfortunately, the optimal gap between bevacizumab and pemetrexed/cisplatin administration in humans has not been determined.To address this need, we have previously developed a robust preclinical mathematical model of BEV-PEM/CIS, and we've used that mathematical model to make a first prediction of optimal BEV-PEM/CIS administration in humans. Mathematical modeling is an indispensable tool for scheduling optimization as it allows the researchers to simulate a large set of in-silico experiments and make practical predictions based on those experiments without the need for considerable time and resource investment in in-vivo studies. Those predictions can then be used to guide future studies, greatly accelerating drug development and optimization.To further refine our model, we kindly request access to previous clinical studies in BEV-PEM/CIS. With this data, we will be able to enhance our model to make better predictions in humans and provide a framework for any researcher working in a similar combination of drugs to make better, data-informed decisions. In addition, this model can be used as a starting point for developing individualized therapy recommendations for patients with NSCLC being treated with BEV-PEM/CIS.

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Statistical Analysis Plan