添加性预测了大多数已批准的结合疗法对晚期癌症的疗效
Haeun Hwangbo1,2, Sarah C Patterson1, Andy Dai3
1Department of Pharmacology, Computational Medicine Program, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
大多数癌症药物组合对无进展生存期 (PFS) 具有附加效应,而不是协同效应. 这表明附加性,而不是协同性,可以指导有效的癌症组合疗法的合理设计.
科学领域:
- 在瘤学瘤学.
- 临床药理学 临床药理学
- 生物统计学 生物统计学
背景情况:
- 晚期癌症通常使用药物组合进行治疗.
- 目前的协同效应指标仅限于临床前数据,阻碍了临床应用.
- 评估临床药物组合疗效需要新的无进展生存 (PFS) 模型.
研究的目的:
- 使用临床数据开发和验证在无进展生存 (PFS) 中药物添加性的模型.
- 为了确定已批准的癌症药物组合是否表现出添加剂或协同效应.
- 评估对临床试验结果的附加性的预测能力.
主要方法:
- 提出了PFS药物添加性的数学模型,结合了患者的可变性和较弱的药物效应.
- 分析了美国食品和药物管理局 (FDA) 批准的治疗晚期癌症的药物组合 (1995-2020).
- 评估了PFS结果的第三阶段临床试验 (2014-2018) 与附加性模型预测相比.
主要成果:
- 95%的FDA批准的治疗晚期癌症的药物组合对PFS表现出添加剂或亚添加剂效应.
- 添加性模型在预测PFS在第三阶段试验中的成功改善方面表现出高灵敏度 (100%).
- 该模型在识别第三阶段试验中可能出现的故障方面表现出良好的特异性 (78%).
结论:
- 协同作用不是临床有效的癌症药物组合的常见或必要特征.
- 添加性是成功组合疗法的可预测和普遍影响.
- 添加性可以作为一种可行的设计原则,用于开发未来的瘤联合疗法.
更多相关视频
12:08Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
08:57Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
Published on: October 5, 2017
相关概念视频
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Agonism and Antagonism: Quantification
To quantify these effects, researchers use a dose-response curve, which provides valuable information about the potency and efficacy of a drug. Potency refers to...
Combined Effects of Drugs: Synergism
Such synergistic combinations...
Dose-Response Relationship: Potency and Efficacy
Tumor Immunotherapy
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
