All-Extremity Exercise as a Novel Strategy for Optimizing Cardiovascular Function during Chemotherapy for Breast Cancer

全肢运动作为乳腺癌化疗期间优化心血管功能的新策略

基本信息

批准号：
10418617
负责人：
Demetra Christou
金额：
$ 19.06万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-07 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10418617
关键词：
Acute Address Adherence Adverse effects Aerobic Exercise Age Air Air Movements Blood Vessels Body Composition Breast Cancer Patient Breast Cancer survivor Cardiomyopathies Cardiotoxicity Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Chemotherapy-Oncologic Procedure Clinical Data Development Disease Dose Echocardiography Elderly Endothelium Equilibrium Event Exercise Exposure to Fatigue Female Financial compensation Foundations Frequencies Functional disorder Heart Rate Heart failure Human Intervention Lead Left Ventricular Ejection Fraction Limb structure Lower Extremity Malignant Neoplasms Measures Mediating Monitor Muscle Weakness Nausea Non-Insulin-Dependent Diabetes Mellitus Nonmetastatic Patient Schedules Patients Personal Satisfaction Phase III Clinical Trials Population Postmenopause Quality of life Randomized Randomized Controlled Clinical Trials Randomized Controlled Trials Regimen Research Resolution Risk Risk Factors Safety Supervision Testing Toxic effect Ultrasonography United States Upper Extremity Walking Work age related brachial artery cardiorespiratory fitness cardiovascular disorder prevention cardiovascular disorder risk chemotherapeutic agent chemotherapy design endothelial dysfunction exercise adherence exercise intervention exercise prescription exercise training fall risk fitness heart function hormone receptor-positive improved innovation malignant breast neoplasm middle age mortality myocardial damage novel novel strategies older patient prevent psychosocial receptor recruit sedentary side effect treadmill treatment as usual

项目摘要

ABSTRACT Currently, there are 3.5 million breast cancer survivors in the United States and this number is expected to increase dramatically. Early stage breast cancer survivors are more likely to die of cardiovascular disease (CVD) than breast cancer. Exposure to chemotherapy may exacerbate existing CVD risk factors or may lead to acute and long-term cardiovascular toxicity. Studies on the cardiovascular impact of chemotherapy have typically focused on acute cardiotoxic effects. However, the vascular impact of chemotherapy, which may have longer term consequences, is not well characterized. Recently, there is increasing evidence that chemotherapy may cause endothelial dysfunction, a key early event in CVD development which leads to loss of atheroprotection and independently predicts CVD events and progression. Therefore, strategies to prevent CVD in breast cancer patients undergoing chemotherapy are clinically important. Aerobic exercise is considered safe during breast cancer chemotherapy and may be an effective strategy for guarding against cardiovascular toxicity but there are limited data in humans and no randomized controlled trials. Acute chemotherapy-induced side effects (e.g., fatigue, muscle weakness, balance problems, increased risk of falls) present unique challenges that may influence the feasibility and tolerability of exercise, and in turn its efficacy. We have recently developed an all- extremity non-weight-bearing exercise (ANE) intervention which is a promising novel and innovative exercise approach for breast cancer patients during chemotherapy and may be superior to other widely recommended forms of exercise. Our central hypothesis is that ANE will be feasible and will lead to greater cardiovascular protection during breast cancer chemotherapy and will be better tolerated than walking. The aims of this exploratory/developmental R21 application are to investigate in patients with primary non-metastatic breast cancer who are undergoing chemotherapy: 1) the effect of ANE, treadmill exercise (TE) and usual care (UC) on endothelial and cardiac function; and 2) the feasibility, tolerability and safety of ANE compared with TE. Breast cancer patients will be randomly assigned to receive 12 weeks of supervised ANE, TE or UC during chemotherapy. Exercise training will be supervised, and exercise prescription will be personalized to their initial fitness level and will gradually progress to 70% of peak heart rate, 50 min/session, 3 days/week. The primary focus will be on endothelial function assessed by brachial artery flow-mediated dilation via high-resolution ultrasonography and global longitudinal strain assessed by speckle tracking echocardiography. Cardiovascular assessments and other study measures will be completed before initiation of chemotherapy and after the intervention. Feasibility, tolerability, and safety will be monitored throughout the intervention. This exploratory/developmental R21 will provide early evidence on whether our promising ANE intervention is feasible, more effective in mitigating cardiovascular toxicity and better tolerated than TE during breast cancer chemotherapy. Our findings will lay the foundation for a Phase III clinical trial.

抽象的目前，美国有350万乳腺癌幸存者，预计这一数字将急剧增加。早期乳腺癌幸存者更有可能死于心血管疾病（CVD）比乳腺癌。接触化疗可能会加剧现有的CVD危险因素，或者可能导致急性和长期心血管毒性。关于化学疗法心血管影响的研究通常已专注于急性心脏毒性作用。但是，化学疗法的血管影响可能更长术语后果，没有很好的特征。最近，有越来越多的证据表明化学疗法可能导致内皮功能障碍，这是CVD开发中的关键早期事件，导致动脉保护失去并独立预测CVD事件和进展。因此，预防CVD乳腺癌的策略接受化疗的患者在临床上很重要。有氧运动在乳房期间被认为是安全的癌症化学疗法，可能是防止心血管毒性的有效策略，但有人类的数据有限，没有随机对照试验。急性化学疗法诱导的副作用（例如疲劳，肌肉无力，平衡问题，增加跌倒的风险）提出了可能的挑战影响运动的可行性和耐受性，进而影响其功效。我们最近开发了一个肢体非重量练习（ANE）干预，这是一项有希望的小说和创新的练习化学疗法期间乳腺癌患者的方法，并且可能优于其他广泛建议运动形式。我们的中心假设是ANE将是可行的，并且会导致更大的心血管在乳腺癌化疗期间的保护，比步行更好。这个目的探索性/发育R21的应用是在原发性非转移性乳房患者中进行调查正在接受化学疗法的癌症：1）ANE，跑步机运动（TE）和常规护理（UC）的影响内皮和心脏功能； 2）与TE相比，ANE的可行性，耐受性和安全性。胸部癌症患者将随机分配接受12周的监督ANE，TE或UC。化学疗法。锻炼训练将受到监督，运动处方将被个性化至最初健身水平，将逐渐发展至峰值心率的70％，50分钟/疗程，每周3天。主要重点将放在通过高分辨率通过臂动脉流介导的扩张评估的内皮功能上通过斑点跟踪超声心动图评估的超声检查和全球纵向应变。心血管评估和其他研究措施将在开始化学疗法之前和之后完成干涉。在整个干预过程中，将监控可行性，耐受性和安全性。这探索性/发展性R21将提供早期证据，表明我们有希望的ANE干预是否是可行的，在减轻心血管毒性方面更有效，并且比乳房期间TE更好癌症化学疗法。我们的发现将为III期临床试验奠定基础。