Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101-Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+early breast cancer using cardiac MRI
Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101-Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+early breast cancer using cardiac MRI
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DOI：
10.1186/1471-2407-11-318
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发表时间：
2011-07-27
期刊：
影响因子：
3.8
通讯作者：
Paterson, Ian
中科院分区：
文献类型：
--
作者：
Pituskin, Edith;Haykowsky, Mark;Paterson, Ian
背景：MANTICORE 101 - 乳腺癌（心脏病学肿瘤学研究中的新疗法的多学科方法）是一项随机试验，旨在确定传统心力衰竭药物疗法（血管紧张素转换酶抑制剂或 β 受体阻滞剂）是否可以预防 HER2+ 早期乳腺癌患者中曲妥珠单抗介导的左心室重构（通过心脏 MRI 测量）。方法/设计：将对 159 名经组织学证实的 HER2+ 乳腺癌患者进行研究参加了平行三臂、随机、安慰剂对照、双盲设计。基线评估后，参与者将以 1:1:1 的比例随机分配至血管紧张素转换酶抑制剂（培哚普利）、β 受体阻滞剂（比索洛尔）或安慰剂。参与者将从曲妥珠单抗治疗前 7 天开始接受为期 1 年的药物或安慰剂。所有组的剂量将根据耐受情况，每隔 1 周系统地增加剂量，总共 3 周。这项随机临床试验的主要目的是确定传统心力衰竭药物治疗是否可以预防 HER2+ 早期乳腺癌患者中曲妥珠单抗介导的左心室重构（通过心脏 MRI 测量左心室舒张末期容积 12 个月的变化来测量）。次要目标包括 1) 确定 HER2+ 早期乳腺癌患者心脏 MRI 上左心室重塑的演变，2) 通过评估血清生物标志物和心脏 MRI 上心肌损伤和细胞凋亡的存在，了解曲妥珠单抗介导的心脏毒性机制，以及 3) 将心肌细胞损伤和细胞外基质重塑的心脏生物标志物与 HER2+ 早期乳腺癌患者心脏 MRI 上左心室重塑相关联癌症讨论：癌症治疗引起的心脏毒性现已被认为是一个日益流行的重大健康问题。据我们所知，MANTICORE 将是第一个测试已证实心力衰竭的随机试验
Background: MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer.Methods/Design: One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer.Discussion: Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure