Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations.
Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations.
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10 种药物-放射组合疗效的临床前数据：评估、担忧和建议。
DOI：
10.1016/j.tranon.2016.01.002
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发表时间：
2016
影响因子：
5
通讯作者：
Brown,JMartin
中科院分区：
文献类型：
--
作者：
Stone,HelenB;Bernhard,EricJ;Coleman,CNorman;Deye,James;Capala,Jacek;Mitchell,JamesB;Brown,JMartin
背景：新治疗干预措施的临床测试需要全面、高质量的临床前数据。最近的报告提出了对临床前数据质量的担忧。本报告检查了 10 种药物与辐射相互作用的数据，并为提高未来研究的质量、可重复性和实用性提供了建议。这些药物是 AZD6244、硼替佐米、17-DMAG、厄洛替尼、吉非替尼、拉帕替尼、奥沙利铂/Lipoxal、舒尼替尼（辉瑞公司总部，纽约州纽约市）、沙利度胺和伏立诺他。 方法：体外和体内数据由 125 篇发表的论文制成，包括方法、辐射和药物剂量、给药方案、结果：在许多情况下，研究包含不充分或不明确的信息，这会妨碍研究的重复或相互比较，并削弱设计和进行临床试验的证据。关于这些药物的已发表报告显示，在增强放射反应方面，结果好坏参半，除了舒尼替尼无效。 结论：需要改进临床前与放射联合使用的候选药物的实验设计、执行和报告。为作者和审稿人提供了一份清单，以确保药物-放射组合的临床前研究符合设计、执行和解释的标准，并报告必要的信息以确保研究的高质量和可重复性。改进的设计、执行、通用的增强措施以及对药物-放射相互作用的临床前研究的一致解释将为临床放射治疗试验的药物优先排序和此类试验的设计提供合理的指导。
BACKGROUND: Clinical testing of new therapeutic interventions requires comprehensive, high-quality preclinical data. Concerns regarding quality of preclinical data have been raised in recent reports. This report examines the data on the interaction of 10 drugs with radiation and provides recommendations for improving the quality, reproducibility, and utility of future studies. The drugs were AZD6244, bortezomib, 17-DMAG, erlotinib, gefitinib, lapatinib, oxaliplatin/Lipoxal, sunitinib (Pfizer, Corporate headquarters, New York, NY), thalidomide, and vorinostat.METHODS:In vitroandin vivodata were tabulated from 125 published papers, including methods, radiation and drug doses, schedules of administration, assays, measures of interaction, presentation and interpretation of data, dosimetry, and conclusions.RESULTS: In many instances, the studies contained inadequate or unclear information that would hamper efforts to replicate or intercompare the studies, and that weakened the evidence for designing and conducting clinical trials. The published reports on these drugs showed mixed results on enhancement of radiation response, except for sunitinib, which was ineffective.CONCLUSIONS: There is a need for improved experimental design, execution, and reporting of preclinical testing of agents that are candidates for clinical use in combination with radiation. A checklist is provided for authors and reviewers to ensure that preclinical studies of drug-radiation combinations meet standards of design, execution, and interpretation, and report necessary information to ensure high quality and reproducibility of studies. Improved design, execution, common measures of enhancement, and consistent interpretation of preclinical studies of drug-radiation interactions will provide rational guidance for prioritizing drugs for clinical radiotherapy trials and for the design of such trials.