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

BMC Cancer

Edith Pituskin²  Mark Haykowsky³  John R Mackey²  Richard B Thompson³  Justin Ezekowitz¹  Sheri Koshman¹  Gavin Oudit¹  Kelvin Chow³  Joseph J Pagano³  Ian Paterson¹ 

[1] Department of Cardiology, Walter McKenzie Center, Edmonton, Alberta, Canada

[2] Cross Cancer Institute, Edmonton, Alberta, Canada

[3] University of Alberta, Edmonton, Alberta, Canada

关键词: Breast cancer;    Trastuzumab;    Cardiac remodeling;    Heart failure;    Cardiotoxicity;   

Others  :  1080817
DOI  :  10.1186/1471-2407-11-318

 received in 2011-06-27, accepted in 2011-07-27,  发布年份 2011

【 摘 要 】

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 pharmacotherapy in the prevention of trastuzumab-mediated cardiotoxicity. We expect the findings of this trial to provide important evidence in the development of guidelines for preventive therapy.

Trial Registration

ClinicalTrials.gov: NCT01016886

【 授权许可】

   
2011 Pituskin et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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