Monoclonal antibodies: state of the art in cardiotoxicity

• Dariya D. Perepechko
• Galina S. Mal’
• Elena B. Artyushkova
• Mikhail P. Gladchenko

Abstract

The cardiotoxicities development on the background of malignant neoplasms therapy is one of the most urgent problem of cardiology and oncology today. The modernized treatment methods, that significantly ease the patient’s condition and prolong life, may be limited due to the occurrence of undesirable side effects on various organs and systems, including cardiovascular. Immunotherapy with monoclonal antibodies is one of the most progressive directions in the malignant neoplasms treatment. This is a class of drugs that have high selectivity with respect to the molecular target. The action mechanism of these substances is quite complex, multi-stage and consists of several processes. These are both compliment-dependent cytotoxicity, and antibody-dependent cellular cytotoxicity, as well as apoptosis induction and the receptors on target cells blocking. The most important risk factors for the side effects development, which affect the cardiovascular system are the anthracycline drugs consumption in anamnesis, from the dosage and time interval during subsequent therapy with monoclonal antibodies. The manifestations of cardiotoxicity are quite variable; These include heart failure, the left ventricular dysfunction development, heart valve lesions, cardiac muscle rhythm and conduction disorders as well as thromboembolism. Most often, patients are diagnosed with arterial hypertension, acute coronary syndrome, which later turns into myocardial infarction, myocarditis or chronic heart failure. Diagnosis of cardiotoxic manifestations mainly includes non-invasive methods: echocardiography, stress echocardiography, electrocardiography, magnetic resonance imaging and determination of blood troponin levels. Treatment of cardiotoxic complications is pathogenetic. In patients with heart failure the use of angiotensin-converting enzyme (ACE) inhibitors in combination with beta blockers should be considered; patients who have arterial hypertension during the treatment of malignant neoplasms are recommended to use ACE inhibitors, dihydropyridine calcium channel blockers and angiotensin receptor blockers, as well as beta blockers; in case of cardiac arrhythmias, patient management should be strictly individual. Prevention of cardiotoxic complications is based on the correction of newly emerging risk factors and treatment of existing cardiovascular pathologies.

Keywords:cardiotoxicity; monoclonal antibodies; trastuzumab; malignant neoplasms; therapy

References

1. Avdeeva Zh.I., Soldatov A.A., Kiselevsky M.V., Medunitsyn N.V. Antitumor monoclonal antibodies. Immunologiya [Immunology]. 2017; 38 (5): 256–70. (in Russian)

2. Vatutin N.T., Sklyannaya E.V., El-Khatib M.A., Taradin G.G. Cardiovascular complications of anticancer therapy: definition, etiology, epidemiology, pathogenesis, classification (part I). Rossiyskiy onkologicheskiy zhurnal [Russian Journal of Cancer]. 2017; 22 (6): 345–50. (in Russian)

3. Yang X., Li X., Yuan M., Tian C., Yang Y., Wang X., et al. Anticancer therapy-induced atrial fibrillation: electrophysiology and related mechanisms. Front Pharmacol. 2018; 9: 1058.

4. Nuriev R.I., Karaulov A.V, Kisielewsky M.V. Novel treatment strategies for patients with cancer: immunotherapeutic approach. Immunologiya [Immunology]. 2017; 38 (1): 39–48. (in Russian)

5. Ovchinnikov A.G., Skorobogatova A.V., Semiglazova T.Yu., Kozyavin N.A., Ageev F.T., Chazova I.E. Cardiotoxicity of trastuzumab: mechanisms of development, diagnosis, treatment. Voprosy oncologii [Problems in Oncology]. 2016; (6): 719–31. (in Russian)

6. Kobalava Zh.D., Shavarova E.K. Hypertension related to the antitumor treatment with angiogenesis inhibitors: an iatrogenic hypertension. Arterial’naya gipertenziya [Arterial Hypertension]. 2018; 24 (4): 384–95. (in Russian)

7. Hiller L., Dunn J. A., Loi S., et al. Adjuvant trastuzumab duration trials in HER2 positive breast cancer – what results would be practice-changing? Persephone investigator questionnaire prior to primary endpoint results. BMC Cancer. 2018; 18 (1): 391.

8. Loibl S., Gianni L. HER2-positive breast cancer. Lancet. 2017; 389 (10 087): 2415–29.

9. Vasyuk Yu.A., Yushchuk E.N., Nesvetov V.V. Cardiooncology: a new challenge of our time. Cardiovascular complications of antitumor treatment. Moscow : Klinmed Konsulting, 2019: 100 p. (in Russian)

10. Chazova I.E., Oshchepkova E.V., Kirillova M.Yu., Stenina M.B. Risk of hypertension development in patients with oncological diseases under anticancer treatment. Consilium Medicum. 2016; 18 (1): 16–20. (in Russian)

11. Vasyuk Yu.A., Shupenina E.Yu., Novosel E.O., Agapov I.S. Heart rhythm and conduction disorders as manifestations of cardiotoxicity of anticancer treatment: myth or reality? Sibirskiy meditsinskiy zhurnal [Siberian Medical Journal]. 2020; 35 (1): 13–21. (in Russian)

12. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017; 67 (1): 7–30.

13. Chazova I.E., Tyulyandin S.A., Vitsenya M.V., et al. Clinical Manual for Diagnosis, prevention and treatment of cardiovascular complications of cancer therapy. Part I. Sistemnye gipertenzii [Systemic Hypertension]. 2017; 14 (3): 6–20. (in Russian)

14. Manrique C.R., Park M., Tiwari N., Plana J.C., Garcia M.J. Diagnostic strategies for early recognition of cancer therapeutics-related cardiac dysfunction. Clin Med Insights Cardiol. 2017; 11: 1–12.

15. Seliverstova D.V., Evsina O.V. Cardiotoxicity of chemotherapy. Serdtse [Heart]. 2016; 15 (1). 50–7. (in Russian)

16. Nicolazzi M.A., Carnicelli A., Fuorlo M., et al. Anthracycline and trastuzumab-induced cardiotoxicity in breast cancer. Eur Rev Med Pharmacol Sci. 2018; 22 (7): 2175–85.

17. Martinello R., Becco P., Vici P., Airoldi M., Del Mastro L., Garrone O., et al. Trastuzumab-related cardiotoxicity in patients with nonlimiting cardiac comorbidity. Breast J. 2019; 25 (3): 444–9.

18. Truschin A.Yu. Trastuzumab-induced cardiotoxicity - interdisciplinary problem of modern medicine. Mezhdunarodniy nauchno-issledovatel’skiy zhurnal [International Research Journal]. 2019: 4 (82): 118–23. (in Russian)

19. Yuan M., Tse G., Zhang Z., Han X., Wu W.K.K., Li G., et al. The incidence of atrial fibrillation with trastuzumab treatment: a systematic review and meta-analysis. Cardiovasc Ther. 2018; 36 (6): e12475.

20. Modesto Dos Santos V., Modesto Dos Santos L.A. Cardiotoxicity in chemotherapeutic agents. Russ Open Med J. 2021; 10: e0106.

21. Lancellotti P., Galderisi M., Donal E., et al. Protocol update and preliminary results of EACVI/HFA Cardiac Oncology Toxicity (COT) Registry of the European Society of Cardiology. ESC Heart Fail. 2017; 4: 312–8.

22. Touyz R.M., Lang N.N., Herrmann J., van den Meiracker A.H., Danser A.H.J. Recent advances in hypertension and cardiovascular toxicities with vascular endothelial growth factor inhibition. Hypertension. 2017l; 70 (2): 220–6.

23. Ky B. Priorities in the cardiovascular care of breast cancer survivors. J Oncol Pract. 2018; 14 (4): 205–11.

24. Riccio G., Coppola C., Piscopo G., et al. Trastuzumab and target-therapy side effects: Is still valid to differentiate anthracycline Type I from Type II cardiomyopathies? Hum Vaccin Immunother . 2016; 12: 1124–31.

25. Osman M., Elkady M. A prospective study to evaluate the effect of paclitaxel on cardiac ejection fraction. Breast Care. 2017; 12 (4): 255–9.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)