Prevention of Cardiotoxicities With Traditional and Novel Chemotherapeutic Agents
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Purpose of Review
This review will discuss strategies to prevent cardiotoxicity associated with chemotherapeutics. Forty years ago, investigators identified dose-dependent cardiotoxicity related to anthracycline-based regimens. Over recent decades, the development of more selective, mechanism-based chemotherapeutics has been associated with both on-target and off-target adverse cardiovascular sequelae.
Strategies to prevent or attenuate cardiotoxicities include limitation of anthracycline dose, appropriate patient selection, referral/access to cardio-oncology programs, early recognition of cardiac side effects, active cardio-surveillance, cardio-protective medical therapy, treatment-specific concerns, and follow-up. The importance of accurate diagnosis of cardiotoxicity is important as false-positive testing may result in inappropriate holding or stopping potentially life-saving chemotherapy. Data to support use of cardio-protective medical therapy to prevent chemotherapy-related cardiotoxicity is modest at best, limited by marginal effect size, small patient numbers, and short follow-up.
The rapid growth in cardio-oncology clinics may facilitate larger multi-center randomized controlled trials in this area.
KeywordsChemotherapy Cardiotoxicity Prevention Anthracycline Cardiomyopathy Heart failure Novel chemotherapeutics
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 4.Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2014;15(10):1063–93.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.• Porta-Sanchez A, Gilbert C, Spears D, Amir E, Chan J, Nanthakumar K, et al. Incidence, diagnosis, and management of QT prolongation induced by cancer therapies: a systematic review. J Am Heart Assoc. 2017;6(12). A systematic review assessing the incidence of QT prolongation for a variety of cancer drugs and the implications in the long term. As there are no formal guidelines in place for monitoring of QT interval during chemotherapy, the author provides a helpful approach to monitoring these patients during their treatment course. Google Scholar
- 12.Cheuk DK, Sieswerda E, van Dalen EC, Postma A, Kremer LC. Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer. Cochrane Database Syst Rev. 2016;23(8):CD008011.Google Scholar
- 13.Venturini M, Michelotti A, Del Mastro L, Gallo L, Carnino F, Garrone O, et al. Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer. J Clin Oncol. 1996;14(12):3112–20.CrossRefPubMedGoogle Scholar
- 14.Asselin BL, Devidas M, Chen L, Franco VI, Pullen J, Borowitz MJ, et al. Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma: a report of the Children’s Oncology Group Randomized Trial Pediatric Oncology Group 9404. J Clin Oncol. 2016;34(8):854–62.CrossRefPubMedGoogle Scholar
- 15.Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017;23(8):628–51.CrossRefPubMedGoogle Scholar
- 16.Henriksen PA. Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention. Heart. 2017.Google Scholar
- 19.Georgakopoulos P, Roussou P, Matsakas E, Karavidas A, Anagnostopoulos N, Marinakis T, et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol. 2010;85(11):894–6.CrossRefPubMedGoogle Scholar
- 21.Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013;61(23):2355–62.CrossRefPubMedGoogle Scholar
- 22.Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37(21):1671–80.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Avila MS, Ayub-Ferreira SM, de Barros Wanderley Junior MR, Cruz FDD, Goncalves Brandao SM, Carvalho Rigaud VO, et al. Carvedilol for prevention of chemotherapy related cardiotoxicity. J Am Coll Cardiol. 2018;3.Google Scholar
- 34.•• Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, et al. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017;35(35):3942–8. A study assessing the long-term outcomes of patients receiving trastuzumab and adjuvant anthracycline or taxane-based chemotherapy. While past studies have revealed early cardiac toxicities from trastuzumab and adjuvant chemotherapy, this study provides new evidence supporting the idea that the combination of these chemotherapies is actually well tolerated in the long term from a functional and symptomatic standpoint. CrossRefPubMedGoogle Scholar
- 35.Pituskin E, Mackey JR, Koshman S, Jassal D, Pitz M, Haykowsky MJ, et al. Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101-breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity. J Clin Oncol. 2017;35(8):870–7.CrossRefPubMedGoogle Scholar
- 36.Wittayanukorn S, Qian J, Westrick SC, Billor N, Johnson B, Hansen RA. Prevention of trastuzumab and anthracycline-induced cardiotoxicity using angiotensin-converting enzyme inhibitors or beta-blockers in older adults with breast cancer. Am J Clin Oncol. 2017.Google Scholar
- 47.Maitland ML, Bakris GL, Black HR, Chen HX, Durand JB, Elliott WJ, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst. 2010;102(9):596–604.CrossRefPubMedPubMedCentralGoogle Scholar
- 58.Armstrong GT, Joshi VM, Ness KK, Marwick TH, Zhang N, Srivastava D, et al. Comprehensive echocardiographic detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer: results from the St. Jude Lifetime Cohort Study. J Am Coll Cardiol. 2015;65(23):2511–22.CrossRefPubMedPubMedCentralGoogle Scholar