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BMC Cancer. 2018 Sep 3;18(1):864. doi: 10.1186/s12885-018-4778-7.

Rationale and design of the Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study: a 3-arm parallel group phase II randomized controlled trial in early breast cancer.

Author information

1
Department of Biomedical Engineering, University of Alberta, 1098 Research Transition Facility, 8308-114 Street, Edmonton, AB, T6G 2V2, Canada. amy.kirkham@ualberta.ca.
2
Department of Medicine, Division of Cardiology, University of Alberta, Edmonton, Canada.
3
Department of Agricultural, Food & Nutrition Science, University of Alberta, Edmonton, Canada.
4
Department of Oncology, University of Alberta, Edmonton, Canada.
5
Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Canada.
6
Faculty of Nursing, University of Alberta, Edmonton, Canada.
7
Department of Biomedical Engineering, University of Alberta, 1098 Research Transition Facility, 8308-114 Street, Edmonton, AB, T6G 2V2, Canada.

Abstract

BACKGROUND:

Anthracycline chemotherapy agents are commonly used to treat breast cancer, but also result in cardiac injury, and potentially detrimental effects to vascular and skeletal muscle. Preclinical evidence demonstrates that exercise and caloric restriction can independently reduce anthracycline-related injury to the heart as well as cancer progression, and may be promising short-term strategies prior to treatment administration. For women with breast cancer, a short-term strategy may be more feasible and appealing, as maintaining regular exercise training or a diet throughout chemotherapy can be challenging due to treatment symptoms and psychosocial distress.

METHODS:

The Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study will determine whether acute application of these interventions shortly prior to receipt of each treatment can reduce anthracycline-related toxicity to the heart, aorta, and skeletal muscle. Fifty-six women with early stage breast cancer scheduled to receive anthracycline treatment will be randomly assigned to one of three groups who will: 1) perform a single, 30-min, vigorous-intensity, aerobic exercise session 24 h prior to each anthracycline treatment; 2) consume a prepared diet reduced to 50% of caloric needs for 48 h prior to each anthracycline treatment; or 3) receive usual cancer care. The primary outcome is magnetic resonance imaging (MRI) derived left ventricular ejection fraction reserve (peak exercise LVEF - resting LVEF) at the end of anthracycline treatment. Secondary outcomes include MRI-derived measures of cardiac, aortic and skeletal muscle structure and function, circulating NT-proBNP, cardiorespiratory fitness and treatment symptoms. Exploratory outcomes include quality of life, fatigue, tumor size (only in neoadjuvant patients), oxidative stress and antioxidants, as well as clinical cardiac or cancer outcomes. MRI, exercise tests, and questionnaires will be administered before, 2-3 weeks after the last anthracycline treatment, and one-year follow-up.

DISCUSSION:

The proposed lifestyle interventions are accessible, low cost, drug-free potential methods for mitigating anthracycline-related toxicity. Reduced toxic effects on the heart, aorta and muscle are very likely to translate to short and long-term cardiovascular health benefits, including enhanced resilience to the effects of subsequent cancer treatment (e.g., radiation, trastuzumab) aging, and infection.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT03131024; 4/21/18.

KEYWORDS:

Anthracyclines; Breast cancer; Caloric restriction; Cardiotoxicity; Exercise; Magnetic resonance imaging

PMID:
30176834
PMCID:
PMC6122558
DOI:
10.1186/s12885-018-4778-7
[Indexed for MEDLINE]
Free PMC Article

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