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

Kirkham, Amy A.; Eves, Neil D.; Shave, Rob; Bland, Kelcey A.; Bovard, Joshua; Gelmon, Karen A.; Virani, Sean; McKenzie, D. C.; Stöhr, Eric J.; Waburton, Darren E R; Campbell, Kristin L.

doi:10.1007/s10549-017-4554-4

Cited by 76 publications

(111 citation statements)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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]. …”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2018

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BackgroundAnthracycline 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.MethodsThe 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.DiscussionThe 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 registrationClinicalTrials.gov NCT03131024; 4/21/18.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…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]. The intensity and timing of exercise with respect to DOX treatment may alter what cardioprotective effect can be achieved and it may be beneficial to assess different exercise protocols in cancer patients on DOX chemotherapy.…”

Section: Exercisementioning

confidence: 95%

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

Timm

Tyler

2020

Cardiovasc Drugs Ther

129

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Doxorubicin is a commonly used chemotherapeutic agent for the treatment of a range of cancers, but despite its success in improving cancer survival rates, doxorubicin is cardiotoxic and can lead to congestive heart failure. Therapeutic options for this patient group are limited to standard heart failure medications with the only drug specific for doxorubicin cardiotoxicity to reach FDA approval being dexrazoxane, an iron-chelating agent targeting oxidative stress. However, dexrazoxane has failed to live up to its expectations from preclinical studies while also bringing up concerns about its safety. Despite decades of research, the molecular mechanisms of doxorubicin cardiotoxicity are still poorly understood and oxidative stress is no longer considered to be the sole evil. Mitochondrial impairment, increased apoptosis, dysregulated autophagy and increased fibrosis have also been shown to be crucial players in doxorubicin cardiotoxicity. These cellular processes are all linked by one highly conserved intracellular kinase: adenosine monophosphate-activated protein kinase (AMPK). AMPK regulates mitochondrial biogenesis via PGC1α signalling, increases oxidative mitochondrial metabolism, decreases apoptosis through inhibition of mTOR signalling, increases autophagy through ULK1 and decreases fibrosis through inhibition of TGFβ signalling. AMPK therefore sits at the control point of many mechanisms shown to be involved in doxorubicin cardiotoxicity and cardiac AMPK signalling itself has been shown to be impaired by doxorubicin. In this review, we introduce different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and we discuss the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity.

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“…Another study showed that eight weeks of endurance exercise prior to chronic induction of ADR could reduce cardiac toxicity by reducing serum LDH levels (26). Kirkham et al suggested that shortterm endurance exercise before treatment of cancer patients with ADR could reduce serum cTnT levels (27). In general, previous reports indicated that endurance exercise could protect the cardiomyocytes against the ADR-induced cardiac toxicity.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Effect of High-Intensity Aerobic Interval Training against Adriamycin-Induced Cardiac Toxicity in Rats

Ebrahimi

Choobineh

Soori

et al. 2019

J Clin Res Paramed Sci

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Background: Adriamycin (ADR) is a useful drug for the treatment of hematologic malignancies and solid tumors. However, its clinical uses are limited due to dose-dependent cardiac toxicity. Contrary to moderate endurance training, there is little research about the protective role of high-intensity aerobic interval training (HIIT) against the ADR-induced cardiac toxicity and its mechanisms. Objectives: The present study aimed to investigate the protective effect of HIIT against ADR-induced cardiac toxicity in the left ventricle of rats by assessment of the serum biomarkers of cardiac injury (LDH and CK-MB). Methods: Twenty-four male Wistar rats were randomly assigned into four groups (n = 6/group): (1) Control; (2) ADR (20 mg/kg.bw); 3) HIIT (7 sets of 4 minutes intervals at 80%-90% VO2max interspersed with 3 minutes periods of 65%-75% VO2max, for 8 weeks), and (4) HIIT + ADR. The ELISA method was used for measuring the serum levels of biomarkers. Statistical differences were analyzed using one-way analysis of variance followed by Tukey's post hoc test for multiple comparisons (α < 0.05). Results: Based on the results, ADR-induction resulted in a significant increase in the LDH and CK-MB levels compared to the ADR group (P < 0.05). Also, the HIIT per se insignificantly increased the levels of LDH and CK-MB compared to the control group. However, the HIIT before ADR-induction resulted in a significant decrease in the LDH and CK-MB levels compared to the ADR group (P < 0.05). Conclusions: Therefore, the HIIT can be a proper non-prescriptive strategy for preventing ADR-induced cardiotoxicity via reducing the serum biomarkers of cardiac injury.

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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

Cited by 76 publications

References 46 publications

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

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

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

Cardioprotective Effect of High-Intensity Aerobic Interval Training against Adriamycin-Induced Cardiac Toxicity in Rats

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