Skip to main content

Advertisement

SpringerLink
Log in

Cardiotoxicity in Hematological Diseases: Are the Tyrosine Kinase Inhibitors Imatinib and Nilotinib Safe?

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Chemotherapy-induced cardiotoxicity is a growing concern. The cardiotoxic impact of new drugs such as tyrosine kinase inhibitors is unknown, especially the ones used for chronic myeloid leukemia. We aim to evaluate nilotinib- and imatinib-induced cardiotoxicity. Single-center prospective study of consecutive patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors was conducted during 2015. Patients underwent an initial clinical, laboratorial and echocardiographic evaluation, repeated after 1 year. Eleven patients were included [60.0 (11) years, 63.6% of males; seven patients treated with imatinib and four with nilotinib]. After 1 year of follow-up, all patients remained in functional NYHA class I, with a similar Minnesota quality of life score. Also there was no difference in the biomarkers evaluated (cystatin-C and NT-proBNP). Likewise, no modification in systolic or diastolic function evaluated by echocardiography was observed. All patients presented normal values of longitudinal, circumferential and radial strain in the baseline study, without changes during follow-up. In addition, there were no differences between the two tyrosine kinase inhibitors used, considering all the aforementioned variables. No clinical, laboratory or echocardiographic evidence of nilotinib- and imatinib-induced cardiotoxicity was observed. However, these results should be confirmed in multicenter studies given the low incidence of chronic myeloid leukemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Yang, B., & Papoian, T. (2012). Tyrosine kinase inhibitor (TKI) induced cardiotoxicity: Approaches to narrow the gaps between preclinical safety evaluation and clinical outcome. Journal of Applied Toxicology, 32(12), 945–951.

    Article  PubMed  CAS  Google Scholar 

  2. Volkova, M., & Russell, R. (2011). Anthracycline cardiotoxicity: Prevalence, pathogenesis and treatment. Current Cardiology Reviews, 7(4), 214–220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Nemeth, B. T., Varga, Z. V., Wu, W. J., & Pacher, P. (2017). Trastuzumab cardiotoxicity: From clinical trials to experimental studies. British Journal of Pharmacology, 174(21), 3727–3748.

    Article  PubMed  CAS  Google Scholar 

  4. Groarke, J. D., Nguyen, P. L., Nohria, A., Ferrari, R., Cheng, S., & Moslehi, J. (2014). Cardiovascular complications of radiation therapy for thoracic malignancies: The role for non-invasive imaging for detection of cardiovascular disease. European Heart Journal, 35(10), 612–623.

    Article  PubMed  Google Scholar 

  5. Krause, D. S., & Van Etten, R. A. (2005). Tyrosine kinases as targets for cancer therapy. New England Journal of Medicine, 353(2), 172–187.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang, J., Yang, P. L., & Gray, N. S. (2009). Targeting cancer with small molecule kinase inhibitors. Nature Reviews Cancer, 9(1), 28–39.

    Article  PubMed  CAS  Google Scholar 

  7. Hartmann, J. T., Haap, M., Kopp, H.-G., & Lipp, H.-P. (2009). Tyrosine kinase inhibitors—A review on pharmacology, metabolism and side effects. Current Drug Metabolism, 10(5), 470–481.

    Article  PubMed  CAS  Google Scholar 

  8. Zamorano, J. L., Lancellotti, P., Rodriguez Munoz, D., Aboyans, V., Asteggiano, R., Galderisi, M., et al. (2016). ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. European Heart Journal, 37(36), 2768–2801.

    Article  PubMed  Google Scholar 

  9. Heath, E. I., Infante, J., Lewis, L. D., Luu, T., Stephenson, J., Tan, A. R., et al. (2013). A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors. Cancer Chemotherapy and Pharmacology, 71(3), 565–573.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Chu, T. F., Rupnick, M. A., Kerkela, R., Dallabrida, S. M., Zurakowski, D., Nguyen, L., et al. (2007). Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet, 370(9604), 2011–2019.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Abdel-Rahman, O., & Fouad, M. (2014). Risk of cardiovascular toxicities in patients with solid tumors treated with sorafenib: An updated systematic review and meta-analysis. Future Oncol, 10(12), 1981–1992.

    Article  PubMed  CAS  Google Scholar 

  12. Force, T., Krause, D. S., & Van Etten, R. A. (2007). Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nature Reviews Cancer, 7(5), 332–344.

    Article  PubMed  CAS  Google Scholar 

  13. Chen, M. H., Kerkelä, R., & Force, T. (2008). Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation, 118(1), 84–95.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Moen, M. D., McKeage, K., Plosker, G. L., & Siddiqui, M. A. A. (2007). Imatinib: A review of its use in chronic myeloid leukaemia. Drugs, 67(2), 299–320.

    Article  PubMed  CAS  Google Scholar 

  15. Keskin, D., Sadri, S., & Eskazan, A. E. (2016). Dasatinib for the treatment of chronic myeloid leukemia: Patient selection and special considerations. Drug Design, Development and Therapy, 10, 3355–3361.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Emole, J., Talabi, T., & Pinilla-Ibarz, J. (2016). Update on the management of Philadelphia chromosome positive chronic myelogenous leukemia: Role of nilotinib. Biologics, 10, 23–31.

    PubMed  PubMed Central  CAS  Google Scholar 

  17. Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Smigal, C., et al. (2016). Cancer statistics, 2006. CA: A Cancer Journal for Clinicians, 56(2), 106–130.

    Google Scholar 

  18. Lang, R. M., Badano, L. P., Mor-Avi, V., Afilalo, J., Armstrong, A., Ernande, L., et al. (2016). Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of, Cardiovascular Imaging. European Heart Journal: Cardiovascular Imaging, 17(4), 412.

    Google Scholar 

  19. Kleijn, S. A., Pandian, N. G., Thomas, J. D., Perez de Isla, L., Kamp, O., Zuber, M., et al. (2015). Normal reference values of left ventricular strain using three-dimensional speckle tracking echocardiography: Results from a multicentre study. European Heart Journal: Cardiovascular Imaging, 16(4), 410–416.

    PubMed  Google Scholar 

  20. Kerkelä, R., Grazette, L., Yacobi, R., Iliescu, C., Patten, R., Beahm, C., et al. (2006). Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nature Medicine, 12(8), 908–916.

    Article  PubMed  CAS  Google Scholar 

  21. Wolf, A., Couttet, P., Dong, M., Grenet, O., Heron, M., Junker, U., et al. (2010). Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies. Leukemia Research, 34(9), 1180–1188.

    Article  PubMed  CAS  Google Scholar 

  22. Herman, E. H., Knapton, A., Rosen, E., Thompson, K., Rosenzweig, B., Estis, J., et al. (2011). A multifaceted evaluation of imatinib-induced cardiotoxicity in the rat. Toxicologic Pathology, 39(7), 1091–1106.

    Article  PubMed  CAS  Google Scholar 

  23. Kaya, Z., & Karanfil, M. (2012). Assessment of left ventricular systolic and diastolic function with conventional and tissue Doppler echocardiography imaging techniques in patients administered tyrosine kinase inhibitor. Turk Kardiyol Dern Arş, 40(7), 597–605.

    Article  PubMed  Google Scholar 

  24. Verstovsek, S., Golemovic, M., Kantarjian, H., Manshouri, T., Estrov, Z., Manley, P., et al. (2005). AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells. Cancer, 104(6), 1230–1236.

    Article  PubMed  CAS  Google Scholar 

  25. Tiwari, A. K., Sodani, K., Wang, S. R., Kuang, Y. H., Ashby, C. R., Jr., Chen, X., et al. (2009). Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochemical Pharmacology, 78(2), 153–161.

    Article  PubMed  CAS  Google Scholar 

  26. Nilotinib, T., Dan, H., Jin, L., & Cheng, L. (2016). Nilotinib reverses ABCB1/P-glycoprotein-mediated multidrug resistance but increases cardiotoxicity of doxorubicin in a MDR xenograft model. Toxicology Letters, 30(259), 124–132.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiology Department, Faculty of Medicine, Santa Maria University Hospital (CHLN), Lisbon Academic Medical Centre and Cardiovascular Centre of the University of Lisbon, Av. Prof. Egas Moniz, 1649-035, Lisbon, Portugal

    Ana Rita G. Francisco, Cláudio David, Fausto J. Pinto & Ana G. Almeida

  2. Hematology Department, Faculty of Medicine, Santa Maria University Hospital (CHLN), Lisbon, Portugal

    Daniela Alves & Lurdes Guerra

Authors
  1. Ana Rita G. Francisco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cláudio David
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lurdes Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fausto J. Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana G. Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Rita G. Francisco.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Francisco, A.R.G., Alves, D., David, C. et al. Cardiotoxicity in Hematological Diseases: Are the Tyrosine Kinase Inhibitors Imatinib and Nilotinib Safe?. Cardiovasc Toxicol 18, 431–435 (2018). https://doi.org/10.1007/s12012-018-9453-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-018-9453-3

Keywords

Search

Navigation