Protective effects of acute exercise prior to doxorubicin on cardiac function of breast cancer patients: A proof-of-concept RCT

Abstract

The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin.

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

“…Based on preclinical evidence [23, 24], we previously investigated the effect of 30 min of vigorous-intensity treadmill walking performed 24 h prior to every anthracycline treatment (i.e., one session per 2–3 week cycle) on markers of cardiotoxicity and treatment symptoms in women with breast cancer [25, 26]. This is a highly feasible approach as patients are usually scheduled to attend the treatment center for blood tests and physician examination the day prior to treatments and this day would also correspond with the nadir of symptoms from the previous treatment.…”

“…Further, the exercise session significantly attenuated NT-proBNP at 24–48 h after the first treatment, which is a circulating biomarker of anthracycline-related cardiac damage and cardiac events. At treatment completion, performing the session prior to each therapy had prevented an increase in resting heart rate (highly prognostic of mortality) and cardiac output, and reduced body weight and prevalence of sore muscles, low back pain and depressed mood relative to usual care [25, 26]. …”

The effect of an aerobic exercise bout 24 h prior to each doxorubicin treatment for breast cancer on markers of cardiotoxicity and treatment symptoms: a RCT

“…In two studies in rodents, a single 60-minute bout of vigorous-intensity treadmill running performed 24 hours prior to doxorubicin treatment completely prevented or attenuated deleterious changes in systolic and diastolic cardiac function, as well as markers of cardiomyocyte oxidative stress, mitochondrial dysfunction, and apoptotic signaling [8,9]. In breast cancer patients, we reported the acute effect of a single 30-minute, vigorous-intensity treadmill walking bout performed 24 hours prior to the first doxorubicin treatment [10]. Relative to usual care, the exercise bout resulted in a significant attenuation of the circulating biomarker that is prognostic for anthracycline-related cardiac injury and events, NT-proBNP, and a 46% absolute risk reduction of this biomarker exceeding a clinical cut-point for overt acute heart failure.…”

“…The randomization sequence was generated by a spreadsheet random function by a party external to the study, and implemented with sequentially numbered envelopes. We previously reported the acute effect of one bout of exercise on cardiac function and biomarkers [10], and here we present the cumulative effects of one exercise bout prior to every treatment on cardiac function, biomarkers, treatment symptoms, as well as other descriptive variables throughout chemotherapy treatment in the same cohort. As acute changes with a single chemotherapy treatment (i.e.…”

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

“…Clinical studies assessing the potential cardioprotective effects of exercise in heart failure in general as well as the cellular and molecular basis of such cardioprotective effects are summarised in reference [150]. In relation to DOX cardiotoxicity, an exercise bout performed 24 h prior to doxorubicin treatment reduced circulating NT-proBNP and increased systolic function in female breast cancer patients indicative of reduced acute DOX cardiotoxicity [151]. However, in the same patient group, exercise did not have an effect on markers of subclinical cardiotoxicity 7-14 days after DOX, even though there was a positive systemic effect on haemodynamics, musculoskeletal symptoms, mood and body weight [152].…”