Dose finding with drug combinations in cancer phase I clinical trials using conditional escalation with overdose control.
Dose finding with drug combinations in cancer phase I clinical trials using conditional escalation with overdose control.
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DOI：
10.1002/sim.6201
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发表时间：
2014-09-28
影响因子：
2
通讯作者：
Rogatko, Andre
中科院分区：
文献类型：
--
作者：
Tighiouart, Mourad;Piantadosi, Steven;Rogatko, Andre
关键词：
我们提出了一个贝叶斯自适应设计的剂量发现的两种药物的组合在癌症I期临床试验。目标是将最大耐受剂量（MTD）估计为二维笛卡尔平面中的曲线。我们使用逻辑模型来描述两种药剂的剂量与剂量限制性毒性的概率之间的关系。根据临床医生可以容易地解释的参数，该模型被重新参数化。试验设计采用单变量递增和过量控制进行，其中在试验的每个阶段，我们使用一种药物的MTD的当前后验分布（给定另一种药物的当前剂量）寻求该药物的剂量。在试验结束时，提出MTD曲线的估计值作为模型参数贝叶斯估计值的函数。我们根据试验设计的安全性和在真实MTD曲线附近的剂量组合推荐百分比来评价设计操作特征。我们还研究了该方法在真实剂量-毒性关系的模型误设下的性能。
We present a Bayesian adaptive design for dose finding of a combination of two drugs in cancer phase I clinical trials. The goal is to estimate the maximum tolerated dose (MTD) as a curve in the two-dimensional Cartesian plane. We use a logistic model to describe the relationship between the doses of the two agents and the probability of dose limiting toxicity. The model is re-parameterized in terms of parameters clinicians can easily interpret. Trial design proceeds using univariate escalation with overdose control, where at each stage of the trial, we seek a dose of one agent using the current posterior distribution of the MTD of this agent given the current dose of the other agent. At the end of the trial, an estimate of the MTD curve is proposed as a function of Bayes estimates of the model parameters. We evaluate design operating characteristics in terms of safety of the trial design and percent of dose recommendation at dose combination neighborhoods around the true MTD curve. We also examine the performance of the approach under model misspecifications for the true dose-toxicity relationship.
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影响因子：
1.9
作者：
Wang, K;Ivanova, A
通讯作者：
Ivanova, A
影响因子：
2.2
作者：
Chen, Zhengjia;Tighiouart, Mourad;Kowalski, Jeanne
通讯作者：
Kowalski, Jeanne
DOI：
10.1097/00000421-200108000-00003
发表时间：
2001-08-01
影响因子：
2.6
作者：
Lokich, J
通讯作者：
Lokich, J
影响因子：
2
作者：
GATSONIS, C;GREENHOUSE, JB
通讯作者：
GREENHOUSE, JB
影响因子：
2
作者：
Shi, Yun;Yin, Guosheng
通讯作者：
Yin, Guosheng