Mitigation of Radiation Pneumonitis and Fibrosis

减轻放射性肺炎和纤维化

• 批准号: 9230807
• 负责人: Eric Phin Cohen
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9230807
• 关键词: Achievement; Address; Adult; Adverse effects; Affect; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Brain; Captopril; Caring; Cessation of life; Clinical; Clinical Research; Clinical Trials; Diagnostic radiologic examination; Dose; Enalapril; FDA approved; Fibrosis; General Population; Health; Heart failure; Human; Injury; Kidney; Kidney Diseases; Laboratory Animals; Laboratory Rat; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Medical; Mission; Modeling; Morbidity - disease rate; National Cancer Institute; Normal tissue morphology; Pathway interactions; Patients; Placebos; Plasma; Pulmonary Inflammation; Quality of life; Radiation; Radiation Fibrosis; Radiation Injuries; Radiation Pneumonitis; Radiation induced damage; Radiation therapy; Rattus; Renin; Renin-Angiotensin System; Reporting; Risk; Severities; Skin; Spinal Cord; Testing; Tissues; Treatment outcome; Veterans; Woman; Work; base; cancer recurrence; cancer survival; cancer therapy; clinical care; hypertension treatment; improved; instrument; irradiation; lung injury; men; mortality; novel strategies; public health relevance; radiation effect; success

DESCRIPTION (provided by applicant): This project will test the effect of enalapril, an angiotensin-converting-enzyme inhibitor, to mitigate radiation pneumonitis and fibrosis in veterans undergoing radiation therapy for lung cancer. It is based on the hypothesis that human normal tissue radiation injury can be safely and effectively mitigated, and on our extensive studies of radiomitigation in experimental animals. Lung cancer is more common in veterans than in the general population; this project is highly relevant to the medical care of veterans. The specific aims are: 1. To test the benefit of enalapril, an angiotensin-converting-enzyme-inhibitor, to mitigate radiation pneumonitis and fibrosis in humans. a. Enalapril or placebo will commence right after the start of irradiation in patients undergoing radiation therapy for lung cancer, and their effects on radiation pneumonitis and fibrosis will be compared. Enalapril will be used rather than captopril, because enalapril is given in single daily doses. 2. To test the mechanism of mitigation of radiation lung injury by enalapril. a. Angiotensinogen, plasma renin activity, and angiotensin II will be measured as renin-angiotensin system markers in all subjects. b. The effect of enalapril on each marker will be assessed, as compared to placebo. 3. To confirm that enalapril in this use does not adversely affect cancer treatment outcomes. a. Cancer recurrence and death from cancer will be compared for the enalapril and placebo groups. These studies will be done in men and women undergoing radiation therapy for lung cancer. Enalapril, or identical-appearing placebo, will be started at the beginning of the radiation treatments. The effect of the enalapril or placebo will be tested by their effect on grade 2 or greater clinical radiation pneumonitis, by their effect on the renin-angiotensin system markers angiotensinogen, plasma renin activity, angiotensin II, and their effect on radiographic evidence of pneumonitis and fibrosis. The broad, long-term objective of our work is to achieve effective and safe mitigation o normal tissue radiation injuries for any tissue type. We and others have successfully mitigated normal tissue radiation injury (NTRI) of kidneys, lungs, skin, and brain, using laboratory rat models. The success of these human studies will have a high impact for subjects at risk of NTRI to the lungs. This will improve the health of veterans with lung cancer, which is highly relevant t the mission of the Department of Veterans Affairs. That success will be a significant impetus to extend the radiomitigation concept to other normal tissues at risk during radiation therapy, such as spinal cord or brain.

描述（由申请人提供）： 该项目将测试依那普利（一种血管紧张素转换 - 酶抑制剂）对正在接受肺癌放射治疗的退伍军人的肺炎和纤维化的作用。这是基于以下假设：人类正常组织辐射损伤可以安全有效地减轻，以及我们对实验动物中放射性的广泛研究。在退伍军人中，肺癌比普通人群更普遍。该项目与退伍军人的医疗保健高度相关。 具体目的是：1。测试的好处 依那普利是一种血管紧张素转换 - 酶抑制剂，可减轻人类的辐射肺炎和纤维化。 一个。依纳普利或安慰剂将在开始辐照后立即开始 接受放射治疗的肺癌的患者，并将比较其对肺炎和纤维化的影响。 依那普利将被使用而不是卡托普利，因为依那瑞利以每日剂量给出。 2。测试依那倍兰氏菌对辐射肺损伤的缓解机制。 一个。血管紧张素原，血浆肾素活性和血管紧张素II 在所有受试者中，将以肾素 - 血管紧张素系统标记来衡量。 b。与安慰剂相比，将评估依拉氏菌对每个标记的影响。 3。确认这种用途中的依那普利不会对癌症治疗结果产生不利影响。 一个。将比较依那瑞利和安慰剂组的癌症复发和死亡。 这些研究将在接受肺癌放射治疗的男性和女性中进行。依那普利或相同的安慰剂将在辐射处理的开头开始。依那普利或安慰剂的作用将通过对2级或更高临床肺炎肺炎的影响来测试，它们对肾素 - 血管紧张素系统的影响标志着血管紧张素原，血浆肾素活性，血管紧张素II及其对肺炎和纤维化的放射线遗传学证据的影响。 我们工作的广泛，长期目标是实现有效，安全的缓解o任何组织类型的正常组织辐射损伤。我们和其他人使用实验室大鼠模型成功地减轻了肾脏，肺，皮肤和大脑的正常组织辐射损伤（NTRI）。这些人类研究的成功将对有NTRI风险的受试者产生很大的影响。这将改善肺癌退伍军人的健康，这与退伍军人事务部的任务非常重要。这种成功将是将放射性概念扩展到放射治疗期间处于危险中的其他正常组织（例如脊髓或大脑）的重要动力。