Innovations for phase I dose-finding designs in pediatric oncology clinical trials.
Innovations for phase I dose-finding designs in pediatric oncology clinical trials.
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DOI：
10.1016/j.cct.2016.01.009
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发表时间：
2016-03
影响因子：
2.2
通讯作者：
Paoletti X
中科院分区：
文献类型：
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作者：
Doussau A;Geoerger B;Jiménez I;Paoletti X
I期肿瘤学临床试验旨在确定将推荐用于II期试验的最佳剂量。在儿科肿瘤学中，这些试验的开展提出了具体的挑战，因为这种疾病很罕见，治疗选择有限。此外，从成人试验中已知耐受性特征。本文提供了一个审查的主要最近的发展，在这些试验的设计，灵感来自需要科普的具体挑战，剂量发现在癌症儿科肿瘤。我们回顾了模拟研究，比较了专门用于解决这些挑战的设计。我们还回顾了2009-2014年期间已发表的儿科肿瘤剂量探索试验中使用的设计。确定了三个主要创新领域。首先，设计是为了放松规则，以更灵活的包容性。第二，纳入成人研究数据的方法。第三，在儿科肿瘤学中解释重复周期的毒性评价的设计。除了这个概述，我们提出了一些进一步的方向设计儿科剂量探索试验。
Phase I oncology clinical trials are designed to identify the optimal dose that will be recommended for phase II trials. In pediatric oncology, the conduct of those trials raise specific challenges, as the disease is rare with limited therapeutic options. In addition, the tolerance profile is known from adult trials. This paper provides a review of the major recent developments in the design of these trials, inspired by the need to cope with the specific challenges of dose finding in cancer pediatric oncology. We reviewed simulation studies comparing designs dedicated to address these challenges. We also reviewed the design used in published dose-finding trials in pediatric oncology over the period 2009–2014. Three main fields of innovation were identified. First, designs that were developed in order to relax the rules for more flexible inclusions. Second, methods to incorporate data emerging from adult studies. Third, designs accounting for toxicity evaluation at repeated cycles in pediatric oncology. In addition to this overview, we propose some further directions for designing pediatric dose-finding trials.