Abstract
BackgroundAnthracyclines (AC), widely used and effective anticancer agents, are known to induce both acute and chronic declines in cardiovascular health, ranging in severity from asymptomatic, subclinical dysfunction to substantial cardiomyopathy leading to congestive heart failure and death. There is substantial evidence that physical activity, higher levels of cardiorespiratory fitness, and exercise therapy can help prevent cardiovascular disease. Moreover, animal studies have shown that exercise performed concomitantly with AC treatment may attenuate early cardiac damage that results from AC exposure. Our primary objective is to assess the feasibility of a 12-week aerobic exercise training (AET) program in patients receiving AC-based chemotherapy.Methods/designThis is a prospective, single-arm (pre-post-test design), feasibility study of a supervised 12-week progressive, light-to-moderate to moderate-to-vigorous intensity AET program for patients (18–65 years) receiving AC chemotherapeutic treatment for a primary/non-recurrent breast cancer or hematological malignancy. Both feasibility (e.g., participant recruitment, program adherence, safety) and intervention outcome (e.g., biological markers of cardiotoxicity, aerobic capacity, quality of life) measures will be collected. The AET program will include two, 45-min community-based exercise sessions (treadmill or cycle) per week for a total of 12 weeks. All exercise sessions will be supervised by trained exercise specialists.DiscussionData from the EXACT study will be evaluated to determine the need to refine patient recruitment methods and general acceptability of the AET program. Preliminary data on the effects of the AET intervention on pertinent cardiac and health outcomes will also be evaluated and used to inform future studies in terms of the most appropriate outcome measure(s) to adopt and sample size estimation.Trial registrationClinicalTrails.gov, NCT02471053
Highlights
Anthracyclines (AC), widely used and effective anticancer agents, are known to induce both acute and chronic declines in cardiovascular health, ranging in severity from asymptomatic, subclinical dysfunction to substantial cardiomyopathy leading to congestive heart failure and death
Perhaps the most prominent of these are the toxic effects on the heart which may lead to cardiac dysfunction and increased risk of cardiovascular disease (CVD) [1]
Data indicate that the magnitude of CVD risk for long-term survivors may exceed the risk of recurrent cancer and represents the leading non-cancer cause of death among survivors of breast cancer and Hodgkin’s disease [2,3,4,5]
Summary
Anthracyclines (AC), widely used and effective anticancer agents, are known to induce both acute and chronic declines in cardiovascular health, ranging in severity from asymptomatic, subclinical dysfunction to substantial cardiomyopathy leading to congestive heart failure and death. Perhaps the most prominent of these are the toxic effects on the heart (cardiotoxicity) which may lead to cardiac dysfunction and increased risk of cardiovascular disease (CVD) [1]. Cancer therapeutics have been associated with a number of long-term cardiac complications such as decreased left ventricular function, hypertension, arrhythmias, cardiac ischemia, pericardial and valvular disease, cardiomyopathy, and congestive heart failure [6, 7]. The adverse effects of AC can be associated with acute, early-onset, and chronic cardiomyocyte injury that can range in severity from asymptomatic subclinical left ventricular dysfunction to significant cardiac impairment and symptomatic heart failure [9]. Several factors underlie the cardiotoxic effects of AC on the heart, the primary causative factor underlying acute cardiotoxicity appears to involve an inflammatory response while the formation of free radicals appears to be related to chronic AC cardiotoxicity [8] both of which can contribute to the development and progression of CVD [11,12,13]
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