Wang Shu, Sayour Elias, Lee Ji-Hyun
Division of Quantitative Sciences, UF Health, Gainesville, FL, USA.
Department of Biostatistics, University of Florida, Gainesville, FL, USA.
J Appl Stat. 2022 Aug 3;50(9):2055-2078. doi: 10.1080/02664763.2022.2105827. eCollection 2023.
Combinational therapy that combines two or more therapeutic agents is very common in cancer treatment. Currently, many clinical trials aim to assess feasibility, safety and activity of combinational therapeutics to achieve synergistic response. Dose-finding for combinational agents is considerably more complex than single agent, because only partial order of dose combinations' toxicity is known. Prototypical phase I designs may not adequately capture this complexity thus limiting identification of the maximum tolerated dose (MTD) of combinational agents. In response, novel phase I clinical trial designs for combinational agents have been extensively proposed. However, with so many available designs, studies that compare their performances and explore the impact of design parameters, along with providing recommendations are limited. We are evaluating available phase I designs that identify a single MTD for combinational agents using simulation studies under various conditions. We are also exploring the influences of different design parameters and summarizing the risks/benefits of each design to provide general guidance in design selection.
在癌症治疗中，将两种或更多治疗药物联合使用的联合疗法非常普遍。目前，许多临床试验旨在评估联合疗法的可行性、安全性和活性，以实现协同反应。联合药物的剂量探索比单一药物要复杂得多，因为仅知道剂量组合毒性的部分顺序。典型的I期设计可能无法充分捕捉这种复杂性，从而限制了联合药物最大耐受剂量（MTD）的确定。作为回应，针对联合药物的新型I期临床试验设计已被广泛提出。然而，尽管有如此多可用的设计，但比较它们性能、探索设计参数影响并提供建议的研究却很有限。我们正在通过在各种条件下的模拟研究，评估用于确定联合药物单一MTD的现有I期设计。我们还在探索不同设计参数的影响，并总结每种设计的风险/益处，以便在设计选择中提供一般指导。
