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Fulminant Vascular and Cardiac Toxicity Associated with Tyrosine Kinase Inhibitor Sorafenib

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Abstract

The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12.63 ng/mL, BNP of 1690 pg/mL, and negative infectious workup. Electrocardiogram showed sinus tachycardia and new pathologic Q waves in the anterior leads. Coronary angiography revealed severe multivessel coronary artery disease. Peripheral angiography revealed severely diseased left anterior and posterior tibial arteries, tibioperoneal trunk, and peroneal artery, and subtotal occlusion of the right posterior tibial artery. Multiple coronary and peripheral drug-eluting stents were implanted. An intra-aortic balloon pump was placed. Cardiac magnetic resonance imaging revealed chronic left ventricular infarction with some viability, 17% ejection fraction, and left ventricular mural thrombi. The patient opted for medical management. Persistent symptoms 9 months later led to repeat angiography, showing total occlusion of the second obtuse marginal artery due to in-stent restenosis with proximal stent fracture, and chronic total occlusion of the right internal iliac artery extending to the pudendal branch. Cardiac positron emission tomography/computed tomography viability study demonstrated viable myocardium, deeming revascularization appropriate. Symptom resolution was obtained with no recurrences. Sorafenib-associated vasculopathy may follow a fulminant course. Multimodality cardiovascular imaging is essential for optimal management.

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References

  1. Abdel-Qadir, H., Ethier, J. L., Lee, D. S., Thavendiranathan, P., & Amir, E. (2017). Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis. Cancer Treat Rev, 53, 120–127.

    Article  CAS  PubMed  Google Scholar 

  2. Steingart, R. M., Bakris, G. L., Chen, H. X., Chen, M. H., Force, T., Ivy, S. P., et al. (2012). Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors. Am Heart J, 163(2), 156–163.

    Article  CAS  PubMed  Google Scholar 

  3. Hall, P. S., Harshman, L. C., Srinivas, S., & Witteles, R. M. (2013). The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC Heart Fail, 1(1), 72–78.

    Article  PubMed  Google Scholar 

  4. Uraizee, I., Cheng, S., & Moslehi, J. (2011). Reversible cardiomyopathy associated with sunitinib and sorafenib. N Engl J Med, 365(17), 1649–1650.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Duran, J. M., Makarewich, C. A., Trappanese, D., Gross, P., Husain, S., Dunn, J., et al. (2014). Sorafenib cardiotoxicity increases mortality after myocardial infarction. Circ Res, 114(11), 1700–1712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Schmidinger, M., Zielinski, C. C., Vogl, U. M., Bojic, A., Bojic, M., Schukro, C., et al. (2008). Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol, 26(32), 5204–5212.

    Article  PubMed  Google Scholar 

  8. Mego, M., Reckova, M., Obertova, J., Sycova-Mila, Z., Brozmanova, K., & Mardiak, J. (2007). Increased cardiotoxicity of sorafenib in sunitinib-pretreated patients with metastatic renal cell carcinoma. Ann Oncol, 18(11), 1906–1907.

    Article  CAS  PubMed  Google Scholar 

  9. Orphanos, G. S., Ioannidis, G. N., & Ardavanis, A. G. (2009). Cardiotoxicity induced by tyrosine kinase inhibitors. Acta Oncol, 48(7), 964–970.

    Article  CAS  PubMed  Google Scholar 

  10. Battipaglia, G., Ruggeri, A., Massoud, R., El Cheikh, J., Jestin, M., Antar, A., et al. (2017). Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia. Cancer, 123(15), 2867–2874.

    Article  CAS  PubMed  Google Scholar 

  11. Tsuzuki, T., Sassa, N., Shimoyama, Y., Morikawa, T., Shiroki, R., Kuroda, M., et al. (2014). Tyrosine kinase inhibitor-induced vasculopathy in clear cell renal cell carcinoma: an unrecognized antitumour mechanism. Histopathology, 64(4), 484–493.

    Article  PubMed  Google Scholar 

  12. Touyz, R. M., Herrmann, S. M. S., & Herrmann, J. (2018). Vascular toxicities with VEGF inhibitor therapies-focus on hypertension and arterial thrombotic events. J Am Soc Hypertens, 12(6), 409–425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shi, V. J., Galan, A., Odell, I. D., & Choi, J. N. (2016). Cutaneous vasculopathy as an adverse effect of the anti-vascular endothelial growth factor agent axitinib. JAMA Dermatol, 152(2), 222–223.

    Article  PubMed  Google Scholar 

  14. Totzeck, M., Mincu, R. I., Mrotzek, S., Schadendorf, D., & Rassaf, T. (2018). Cardiovascular diseases in patients receiving small molecules with anti-vascular endothelial growth factor activity: a meta-analysis of approximately 29,000 cancer patients. Eur J Prev Cardiol, 25(5), 482–494.

    Article  PubMed  Google Scholar 

  15. Arima, Y., Oshima, S., Noda, K., Fukushima, H., Taniguchi, I., Nakamura, S., et al. (2009). Sorafenib-induced acute myocardial infarction due to coronary artery spasm. J Cardiol, 54(3), 512–515.

    Article  PubMed  Google Scholar 

  16. Wu, S., Chen, J. J., Kudelka, A., Lu, J., & Zhu, X. (2008). Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol, 9(2), 117–123.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Daryl Sudasena, Salman Arain & K. Lance Gould

  2. Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, 1451, 77030, Houston, TX, USA

    Dinu Valentin Balanescu, Teodora Donisan, Saamir Hassan, Nicolas Palaskas, Peter Kim, Kaveh Karimzad, Juan Lopez-Mattei & Cezar Iliescu

Authors
  1. Daryl Sudasena
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  2. Dinu Valentin Balanescu
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  3. Teodora Donisan
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  4. Saamir Hassan
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  5. Nicolas Palaskas
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  6. Peter Kim
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  9. Salman Arain
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  10. K. Lance Gould
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  11. Cezar Iliescu
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Correspondence to Cezar Iliescu.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from the patient presented in this work.

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Handling Editor: John Allen Crow.

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Sudasena, D., Balanescu, D.V., Donisan, T. et al. Fulminant Vascular and Cardiac Toxicity Associated with Tyrosine Kinase Inhibitor Sorafenib. Cardiovasc Toxicol 19, 382–387 (2019). https://doi.org/10.1007/s12012-018-9499-2

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  • DOI: https://doi.org/10.1007/s12012-018-9499-2

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