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.
Study Goal
The researchers aimed to determine whether acute caloric restriction or exercise prior to anthracycline treatment could reduce toxicity to the heart, aorta, and skeletal muscle, including potential effects on oxidative stress and antioxidants.
Results Summary
The abstract does not report specific findings on antioxidants, as the study is described as ongoing with outcomes to be measured post-intervention and at follow-up.
Population
Fifty-six women with early-stage breast cancer scheduled for anthracycline treatment.
Effective Dosage
Not specified for antioxidants (caloric restriction involved 50% of caloric needs for 48 hours prior to treatment).
Duration
Interventions (exercise or caloric restriction) were applied prior to each anthracycline treatment; follow-up included assessments up to one year.
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
exercise | decrease | anthracycline-related injury to the heart | - | - | can independently reduce | #1 |
exercise | decrease | cancer progression | - | - | can independently reduce | #2 |
caloric restriction | decrease | anthracycline-related injury to the heart | - | - | can independently reduce | #3 |
caloric restriction | decrease | cancer progression | - | - | can independently reduce | #4 |
a single, 30-min, vigorous-intensity, aerobic exercise session 24 h prior to each anthracycline treatment | decrease | anthracycline-related toxicity to the heart, aorta, and skeletal muscle | women with early stage breast cancer scheduled to receive anthracycline treatment | - | can reduce | #5 |
a prepared diet reduced to 50% of caloric needs for 48 h prior to each anthracycline treatment | decrease | anthracycline-related toxicity to the heart, aorta, and skeletal muscle | women with early stage breast cancer scheduled to receive anthracycline treatment | 50% | can reduce | #6 |
The proposed lifestyle interventions | decrease | anthracycline-related toxicity | - | - | are potential methods for mitigating | #7 |
Reduced toxic effects on the heart, aorta and muscle | increase | short and long-term cardiovascular health benefits | - | - | are very likely to translate to | #8 |
Reduced toxic effects on the heart, aorta and muscle | increase | enhanced resilience to the effects of subsequent cancer treatment (e.g., radiation, trastuzumab) aging, and infection | - | - | are very likely to translate to | #9 |
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.