Cardioprotective interventions for cancer patients receiving anthracyclines

Dalen, EC van; Kremer, L. C. M.

doi:10.1002/14651858.cd003917

Cited by 7 publications

(7 citation statements)

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“…To our knowledge, this is the first study to characterize the beneficial effect of RRx-001 in doxorubicin-induced cardiotoxicity, a well-known and serious limitation to the clinical use of DOX that adversely impacts the quality of life and overall survival since it is a dose-dependent phenomenon, with damage typically occurring at cumulative doses that exceed 450–550 mg/m 2 . In over 30 years, dexrazoxane, a treatment with serious limitations, not the least of which is its potential to possibly impair the antitumor activity of doxorubicin, remains the only approved FDA agent to reduce the off-target toxicities of anthracyclines in adult women with breast cancer only who have already received a cumulative dose of 300 mg/m 2 . While the renin-angiotensin system (RAS) has been reported to mediate anthracycline-induced cardiotoxicity and the administration of angiotensin receptor blockers (ARBs) to protect against it, the known antioxidant properties of ARBs and ACE-inhibitors may also theoretically counteract the chemotherapeutic effects on tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Effect of Phase 3 Clinical Anticancer Agent, RRx-001, in Doxorubicin-Induced Acute Cardiotoxicity in Mice

et al. 2019

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Anthracycline chemotherapy (e.g., doxorubicin or DOX) is associated with a cumulative dose-dependent cardiac dysfunction that may lead to congestive heart failure, which limits both its use and usefulness in the clinic. The cardiotoxicity may manifest acutely and/or months or years after treatment with doxorubicin has ended. Experimental and human data have demonstrated that angiotensin-converting enzyme/angiotensin-receptor antagonists mediate a cardioprotective effect against anthracycline toxicity. In this study, with the angiotensin receptor blocker, candesartan, as a positive control, we evaluated whether pretreatment with the hypoxic nitric oxide generating anticancer agent, RRx-001, could reduce acute DOX-induced cardiotoxicity. A total of 24 BALB/c mice were randomized for prophylactic treatment with vehicle, RRx-001, candesartan, or no-intervention control. Within each of the three intervention arms, mice received treatment with DOX. Murine pressure–volume analysis was performed with microconductance catheters to characterize the degree of cardiovascular dysfunction within each group. The following hemodynamic parameters were monitored: left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase of left ventricular pressure (±dP/dt max). Five days after doxorubicin injection, untreated (with RRx-001) mice displayed significantly impaired systolic (LVSP, −27%; dP/dt max, −25%; left ventricular developed pressure (LVDP), +33%; P < 0.05) and global (stroke volume (SV), −52%; ejection fraction (EF), −20%; stroke work (SW), −62.5%; heart rate (HR), −18%; cardiac output (CO), −57%; mean blood arterial pressure (MAP), −30%; systemic vascular resistance (SVR), +20%; P < 0.05) LV functions when compared with the untreated (with RRx-001) group. In contrast, RRx-001-treated mice showed improved variables of systolic (LVSP, +27%; dP/dt max, +25%; LVDP, −33%; P < 0.05) and global (SV, +52%; EF, +20%; SW, +62.5%; HR, +18%; CO, +57%; MAP, +30%; SVR, −20%; P < 0.05) LV functions compared with untreated doxorubicin mice. Similar to the positive control, candesartan, the cardiotoxic effects of DOX in mice were partially attenuated by the prophylactic administration of RRx-001. These results suggest that RRx-001 as a multifunctional anticancer agent, which sensitizes cancer cells to the cytotoxic effects of chemotherapy and radiation, may also have beneficial cardioprotective effects.

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Section: Discussionmentioning

confidence: 99%

Cardioprotective Effect of Phase 3 Clinical Anticancer Agent, RRx-001, in Doxorubicin-Induced Acute Cardiotoxicity in Mice

et al. 2019

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“…The absence of well-designed studies impedes the establishment of precise screening and intervention guidelines, highlighting the necessity for collaboration among medical organizations. Informative studies are indispensable prior to the establishment of quality indicators, emphasizing the significance of robust research in guiding oncology and medical practices [18,19].…”

Section: Reviewmentioning

confidence: 99%

Unpacking Trastuzumab-Induced Cardiomyopathy: A Cardiac Conundrum

Peshin,

Modi,

Namburu

et al. 2024

Hearts

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Cardiovascular diseases are a leading cause of mortality in the United States. The increasing number of cancer patients experiencing cardiovascular side effects from chemotherapeutic drugs is a cause for concern. Trastuzumab is a highly effective targeted therapy for HER2-positive cancers but its use is limited globally due to its cardiotoxic effects. The most severe adverse effect is cardiomyopathy, which is characterized by contractile dysfunction and reduced left ventricular systolic function. The electrophysiological side effects of trastuzumab are still not fully understood. Due to these life-threatening side effects, trastuzumab is routinely discontinued. This review aims to provide a comprehensive overview of trastuzumab-induced cardiomyopathy, including the mechanisms by which trastuzumab exerts its cardiotoxic effects, the clinical manifestations, diagnostic strategies, and potential interventions to protect the heart. By shedding light on the various aspects of this condition, we hope to emphasize the importance of early detection and effective management, as well as the urgent need for further research to optimize the balance between successful cancer treatment and cardiovascular well-being. Cardiologists, oncologists, and researchers are at the forefront of this critical intersection between oncology and cardiology, working collaboratively to enhance patient outcomes in the era of trastuzumab therapy.

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“…Dexrazoxane is protective against anthracycline cardiotoxicity by mediating topoisomerase 2β. Its effectiveness has been well established in numerous clinical trials, although two controversies limit its widespread adoption 4, 12 . There was initial evidence that the use of dexrazoxane decreased anti-neoplastic efficacy and although this did not hold up in meta-analysis, the U.S. Food and Drug Administration has approved its use only in patients who have already received at least 300 mg/m 2 of doxorubicin for metastatic breast cancer 12, 13 .…”

Section: Anthracyclinesmentioning

confidence: 99%

“…Its effectiveness has been well established in numerous clinical trials, although two controversies limit its widespread adoption 4, 12 . There was initial evidence that the use of dexrazoxane decreased anti-neoplastic efficacy and although this did not hold up in meta-analysis, the U.S. Food and Drug Administration has approved its use only in patients who have already received at least 300 mg/m 2 of doxorubicin for metastatic breast cancer 12, 13 . In a pediatric population receiving simultaneous etoposide and doxorubicin, there is evidence of an increased risk for secondary malignancies, potentially due to genetic instability 14 .…”

Section: Anthracyclinesmentioning

confidence: 99%

Cardio-oncology: management of cardiovascular toxicity

Markman

2019

F1000Res

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Traditional chemotherapeutic agents and newer targeted therapies for cancer have the potential to cause cardiovascular toxicities. These toxicities can result in arrhythmias, heart failure, vascular toxicity, and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and management strategies to employ when these toxicities occur. While anti-neoplastic therapy occasionally must be discontinued in this setting, it can often be maintained with caution and careful monitoring. In the second of this two-part review series, we focus on the management of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

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Cardioprotective interventions for cancer patients receiving anthracyclines

Cited by 7 publications

References 0 publications

Cardioprotective Effect of Phase 3 Clinical Anticancer Agent, RRx-001, in Doxorubicin-Induced Acute Cardiotoxicity in Mice

Cardioprotective Effect of Phase 3 Clinical Anticancer Agent, RRx-001, in Doxorubicin-Induced Acute Cardiotoxicity in Mice

Unpacking Trastuzumab-Induced Cardiomyopathy: A Cardiac Conundrum

Cardio-oncology: management of cardiovascular toxicity

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