Lai Xiulan, Friedman Avner
Institute for Mathematical Sciences, Renmin University of China, Beijing, People's Republic of China.
Mathematical Bioscience Institute & Department of Mathematics, Ohio State University, Columbus, OH, USA.
BMC Syst Biol. 2019 Mar 13;13(1):30. doi: 10.1186/s12918-019-0706-y.
One of the questions in the design of cancer clinical trials with combination of two drugs is in which order to administer the drugs. This is an important question, especially in the case where one agent may interfere with the effectiveness of the other agent.
In the present paper we develop a mathematical model to address this scheduling question in a specific case where one of the drugs is anti-VEGF, which is known to affect the perfusion of other drugs. As a second drug we take anti-PD-1. Both drugs are known to increase the activation of anticancer T cells. Our simulations show that in the case where anti-VEGF reduces the perfusion, a non-overlapping schedule is significantly more effective than a simultaneous injection of the two drugs, and it is somewhat more beneficial to inject anti-PD-1 first.
The method and results of the paper can be extended to other combinations, and they could play an important role in the design of clinical trials with combination therapy, where scheduling strategies may significantly affect the outcome.
在设计两种药物联合使用的癌症临床试验时，其中一个问题是药物的给药顺序。这是一个重要问题，特别是在一种药物可能会干扰另一种药物疗效的情况下。
在本文中，我们建立了一个数学模型来解决特定情况下的给药顺序问题，即其中一种药物是抗血管内皮生长因子（anti-VEGF）药物，已知它会影响其他药物的灌注。我们选择抗程序性死亡蛋白1（anti-PD-1）作为第二种药物。两种药物都已知可增加抗癌T细胞的活化。我们的模拟表明，在抗VEGF降低灌注的情况下，非重叠给药方案比同时注射两种药物显著更有效，并且先注射抗PD-1在某种程度上更有益。
本文的方法和结果可扩展到其他联合用药情况，并且它们在联合治疗临床试验设计中可能发挥重要作用，其中给药策略可能会显著影响结果。
