The cardiac safety during treatment with sunitinib and sorafenib, multikinase angiogenesis inhibitors Review article
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Published:
Jun 29, 2012
Keywords:
angiogenesis inhibitors, cardiotoxcity, heart failure, arterial and venous thromboembolic events
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Abstract
Cardiotoxicity of multikinase angiogenesis inhibitors, sunitinib and sorafenib, is most often myocardial systolic dysfunction or arterial and venous thromboembolic events. Essential risk factor seems to be iatrogenic arterial hypertension, which is a typical (“class effect”) vascular complication and a predictive factor of the anticancer efficiency. A biochemical and molecular aspect is associated with cardiomyocytes damage and endothelial dysfunction. Specific primary cardioprotective options are still unknown. It was shown the real risk of cardiotoxicity of multikinase angiogenesis inhibitors, sunitinib and sorafenib, in relation to the risk of cardiotoxicity of bevacizumab, the monoclonal antibody anti-VEGF.
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Szmit S. The cardiac safety during treatment with sunitinib and sorafenib, multikinase angiogenesis inhibitors. OncoReview [Internet]. 2012Jun.29 [cited 2024Jul.3];2(2(6):134-42. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/307
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Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
1. Cheng H., Force T.: Why do kinase inhibitors cause cardiotoxicity and what can be done about it? Prog. Cardiovasc. Dis. 2010 Sep-Oct; 53(2): 114-20.
2. National Cancer Institute: Common Toxicity Criteria version 3. Online: http://ctep.cancer.gov/protocol development/electronic_applications/docs/ctcaev3.pdf.
3. Yancik R., Wesley M.N., Ries L.A. et al.: Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer 1998; 82: 2123-2134.
4. Yancik R., Wesley M.N., Ries L.A. et al.: Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 2001; 285: 885-892.
5. Anderson B., Sawyer D.B.: Predicting and preventing the cardiotoxicity of cancer therapy. Expert Rev. Cardiovasc. Ther. 2008; 6: 1023-1033.
6. Mulrooney D.A., Yeazel M.W., Kawashima T. et al.: Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 2009; b4606: 339.
7. Yeh E.T., Bickford C.L.: Cardiovascular complications of cancer therapy: incidence, pathogenesis,diagnosis, and management. J. Am. Coll. Cardiol. 2009; 53: 2231-2247.
8. Maitland M.L., Bakris G.L., Black H.R. et al.: Cardiovascular Toxicities Panel, Convened by the Angiogenesis Task Force of the National Cancer Institute Investigational Drug Steering Committee. Initial Assessment, Surveillance, and Management of Blood Pressure in Patients Receiving Vascular Endothelial Growth Factor Signaling Pathway Inhibitors. J. Natl. Cancer Inst. 2010; 102: 596-604.
9. Chu T.F., Rupnick M.A., Kerkela R., Dallabrida S.M., Zurakowski D., Nguyen L. et al.: Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007; 370: 2011-2019.
10. Will Y., Dykens J.A., Nadanaciva S., Hirakawa B., Jamieson J., Marroquin L.D. et al.: Effect of the multitargeted tyrosine kinase inhibitors imatinib, dasatinib, sunitinib, and sorafenib on mitochondrial function in isolated rat heart mitochondria and H9c2 cells. Toxicol. Sci. 2008; 106: 153-161.
11. Gupta R., Maitland M.L.: Sunitinib, hypertension, and heart failure: a model for kinase inhibitor-mediated cardiotoxicity. Curr. Hypertens. Rep. 2011; 13(6): 430-5.
12. Launay-Vacher V., Deray G.: Hypertension and proteinuria: a class-effect of antiangiogenic therapies. Anticancer Drugs 2009 Jan; 20(1): 81-2.
13. Sica D.A.: Angiogenesis inhibitors and hypertension: an emerging issue. J. Clin. Oncol. 2006; 24: 1329-31.
14. Rini B.I., Cohen D.P., Lu D.R., Chen I., Hariharan S., Gore M.E., Figlin R.A., Baum M.S., Motzer R.J.: Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J. Natl. Cancer Inst. 2011 May 4; 103(9): 763-73.
15. Jain L., Sissung T.M., Danesi R. et al.: Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib. J. Exp. Clin. Cancer Res. 2010 Jul 14; 29: 95.
16. Ravaud A., Sire M.: Arterial hypertension and clinical benefit of sunitinib, sorafenib and bevacizumab in first and second-line treatment of metastatic renal cell cancer. Ann. Oncol. 2009; 20(5): 966-7.
17. Szmit S., Langiewicz P., Zołnierek J., Nurzyński P., Zaborowska M., Filipiak K.J., Opolski G., Szczylik C.: Hypertension as a predictive factor for survival outcomes in patients with metastatic renal cell carcinoma treated with sunitinib after progression on cytokines. Kidney Blood Press. Res. 2012; 35(1): 18-25.
18. Rutkowski P., Bylina E., Switaj T. et al.: An analysis of arterial hypertension and mutational status as predictive factors for results of sunitinib (SU) therapy in gastrointestinal stromal tumors (GIST). ASCO Meeting Abstracts 2011; 29(15 Suppl): 10017.
19. Szmit S., Zaborowska M., Waśko-Grabowska A., Zołnierek J., Nurzyński P., Filipiak K.J., Opolski G., Szczylik C.: Cardiovascular Comorbidities for Prediction of Progression-Free Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Sorafenib. Kidney Blood Press. Res. 2012 Jun 6; 35(6): 468-476.
20. Force T., Krause D.S., Van Etten R.A.: Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat. Rev. Cancer 2007; 7: 332-344.
21. Izumiya Y., Shiojima I., Sato K., Sawyer D.B., Colucci W.S., Walsh K.: Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Hypertension 2006; 47: 887-893.
22. Kamba T., Tam B.Y., Hashizume H., Haskell A., Sennino B., Mancuso M.R. et al.: VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am. J. Physiol. Heart Circ. Physiol. 2006; 290: H560-H576.
23. Chintalgattu V., Ai D., Langley R.R. et al.: Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to loadinduced stress. J. Clin. Invest. 2010; 120: 472-484.
24. Kerkela R., Woulfe K.C., Durand J.B. et al.: Sunitinib-induced cardiotoxicity is mediated by offtarget inhibition of AMP-activated protein kinase. Clin. Transl. Sci. 2009; 2: 15-25.
25. Kappers M.H., van Esch J.H., Sleijfer S., Danser A.H., van den Meiracker A.H.: Cardiovascular and renal toxicity during angiogenesis inhibition: clinical and mechanistic aspects. J. Hypertens. 2009 Dec; 27(12): 2297-309.
26. Motzer R.J., Hutson T.E., Tomczak P., Michaelson M.D., Bukowski R.M., Rixe O. et al.: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 2007; 356: 115-124.
27. Motzer R.J., Michaelson M.D., Redman B.G., Hudes G.R., Wilding G., Figlin R.A. et al.: Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 2006; 24: 16-24.
28. Demetri G.D., van Oosterom A.T., Garrett C.R., Blackstein M.E., Shah M.H., Verweij J. et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomized controlled trial. Lancet 2006; 368: 1329-1338.
29. Khakoo A.Y., Kassiotis C.M., Tannir N., Plana J.C., Halushka M., Bickford C. et al.: Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer 2008; 112: 2500-2508.
30. Schmidinger M., Zielinski C.C., Vogl U.M., Bojic A., Bojic M., Schukro C. et al.: Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 2008; 26: 5204-5212.
31. Telli M.L., Witteles R.M., Fisher G.A., Srinivas S.: Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann. Oncol. 2008; 19: 1613-8.
32. Karp J.E., Gojo I., Pili R., Gocke C.D., Greer J., Guo C. et al.: Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-darabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clin. Cancer Res. 2004; 10: 3577-3585.
33. Petrini I., Lencioni M., Ricasoli M., Iannopollo M., Orlandini C., Oliveri F., Bartolozzi C., Ricci S.: Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma. Cancer Chemother. Pharmacol. 2012 Mar; 69(3): 773-80.
34. Toubert M.E., Vercellino L., Faugeron I., Lussato D., Hindie E., Bousquet G.: Fatal heart failure after a 26-month combination of tyrosine kinase inhibitors in a papillary thyroid cancer. Thyroid 2011 Apr; 21(4): 451-4.
35. Tolcher A.W., Appleman L.J., Shapiro G.I., Mita A.C., Cihon F., Mazzu A., Sundaresan P.R.: A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer. Cancer Chemother. Pharmacol. 2011; 67(4): 751-64.
36. Kamada P., Dudek A.Z.: Sorafenib therapy for metastatic renal carcinoma in patients with low cardiac ejection fraction: report of two cases and literature review. Cancer Invest. 2010; 28: 501-4.
37. Wong M.K., Jarkowski A.: Response to sorafenib after sunitinib-induced acute heart failure in a patient with metastatic renal cell carcinoma: case report and review of the literature. Pharmacotherapy 2009; 29: 473-8.
38. Sablin M.P., Bouaita L., Balleguier C., Gautier J., Celier C., Balcaceres J.L. et al.: Sequential use of sorafenib and sunitinib in renal cancer: Retrospective analysis in 90 patients (Abstract). J. Clin. Oncol. 2007; 25(18 Suppl.): 5038.
39. French K.J., Coatney R.W., Renninger J.P., Hu C.X., Gales T.L., Zhao S., Storck L.M., Davis C.B., McSurdy-Freed J., Chen E., Frazier K.S.: Differences in effects on myocardium and mitochondria by angiogenic inhibitors suggest separate mechanisms of cardiotoxicity. Toxicol. Pathol. 2010; 38(5): 691-702.
40. Garcipérez de Vargas F.J., Gómez-Barrado J.J., Ortiz C., Mendoza J., Sánchez-Calderón P., Marcos G.: Refractory heart failure in a patient treated with bevacizumab. Med. Intensiva. 2012. Online .
41. Hawkes E.A., Okines A.F., Plummer C., Cunningham D.: Cardiotoxicity in patients treated with bevacizumab is potentially reversible. J. Clin. Oncol. 2011 Jun 20; 29(18): e560-2.
42. Szmit S., Nurzyński P., Szaluś N., Opolski G., Szczylik C.: Reversible myocardial dysfunction in a young woman with metastatic renal cell carcinoma treated with sunitinib. Acta Oncol. 2009; 48(6): 921-5.
43. Choueiri T.K., Mayer E.L., Je Y., Rosenberg J.E., Nguyen P.L., Azzi G.R., Bellmunt J., Burstein H.J., Schutz F.A.: Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J. Clin. Oncol. 2011 Feb 20; 29(6): 632-8.
44. Richards C.J., Je Y., Schutz F.A., Heng D.Y., Dallabrida S.M., Moslehi J.J., Choueiri T.K.: Incidence and risk of congestive heart failure in patients with renal and nonrenal cell carcinoma treated with sunitinib. J. Clin. Oncol. 2011 Sep 1; 29(25): 3450-6.
45. Ewer M.S., Suter T.M., Lenihan D.J. et al.: Cardiovascular adverse events (CV-AES) in a pooled analysis of 1090 patients (PT) from phase 3 suntinib (SU) trials. Ann. Oncol. 2010; 21(suppl 8): viii166 (abstr. 506P).
46. Khorana A.A., Francis C.W., Culakova E. et al.: Thromboembolism is a leading cause of death in cancer patients receiving chemotherapy. J. Thromb. Haemost. 2007; 5: 632-634.
47. Chew H.K., Wun T., Harvey D., Zhou H., White R.H.: Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch. Intern. Med. 2006 Feb 27; 166(4): 458-64.
48. Prandoni P., Lensing A.W., Piccioli A., Bernardi E., Simioni P., Girolami B., Marchiori A., Sabbion P., Prins M.H., Noventa F., Girolami A.: Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002 Nov 15; 100(10): 3484-8.
49. Alikhan R., Cohen A.T., Combe S., Samama M.M., Desjardins L., Eldor A., Janbon C., Leizorovicz A., Olsson C.G., Turpie A.G.; MEDENOX Study: Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch. Intern. Med. 2004; 164(9): 963-8.
50. Prandoni P.: Cancer and thromboembolic disease: how important is the risk of thrombosis? Cancer Treat. Rev. 2002; 28: 133-136.
51. Fisher B., Costantino J.P., Wickerham D.L., Redmond C.K., Kavanah M., Cronin W.M., Vogel V., Robidoux A., Dimitrov N., Atkins J., Daly M., Wieand S., Tan-Chiu E., Ford L., Wolmark N.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl. Cancer Inst. 1998 Sep 16; 90(18): 1371-88.
52. Saphner T., Tormey D.C., Gray R.: Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. J. Clin. Oncol. 1991; 9(2): 286-94.
53. Blom J.W., Vanderschoot J.P., Oostindiër M.J. et al.: Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J. Thromb. Haemost. 2006; 4: 529-35.
54. Khorana A.A., Francis C.W., Culakova E. et al.: Risk factors for chemotherapy-induced venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-2829.
55. Heit J.A., Silverstein M.D., Mohr D.N. et al.: Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch. Intern. Med. 2000; 160: 809-15.
56. Khorana A.A., Kuderer N.M., Culakova E., Lyman G.H., Francis C.W.: Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111(10): 4902-7.
57. Elice F., Rodeghiero F., Falanga A., Rickles F.R.: Thrombosis associated with angiogenesis inhibitors. Best Pract. Res. Clin. Haematol. 2009; 22: 115--128.
58. Nalluri S.R., Chu D., Keresztes R., Zhu X., Wu S.: Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008; 300: 2277-2285.
59. Scappaticci F.A., Skillings J.R., Holden S.N. et al.: Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J. Natl. Cancer Inst. 2007; 99: 1232-1239.
60. Ranpura V., Hapani S., Chuang J. et al.: Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis in bevacizumab in cancer patients: A meta-analysis of randomized controlled trials. Acta Oncol. 2010; 49: 287-297.
61. Kuenen B.C., Levi M., Meijers J.C., Kakkar A.K., van Hinsbergh V.W., Kostense P.J. et al.: Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1500-1505.
62. Naib T., Steingart R.M., Chen C.L.: Sorafenib-associated multivessel coronary artery vasospasm. Herz. 2011 Jun; 36(4): 348-51.
63. Arima Y., Oshima S., Noda K., Fukushima H., Taniguchi I., Nakamura S., Shono M., Ogawa H.: Sorafenib-induced acute myocardial infarction due to coronary artery spasm. J. Cardiol. 2009 Dec; 54(3): 512-5.
64. Pantaleo M.A., Mandrioli A., Saponara M., Nannini M., Erente G., Lolli C., Biasco G.: Development of coronary artery stenosis in a patient with metastatic renal cell carcinoma treated with sorafenib. BMC Cancer 2012 Jun 11; 12(1): 231.
65. Choueiri T.K., Schutz F.A., Je Y., Rosenberg J.E., Bellmunt J.: Risk of Arterial Thromboembolic Events With Sunitinib and Sorafenib: A Systematic Review and Meta-Analysis of Clinical Trials. J. Clin. Oncol. 2010 May 1; 28(13): 2280-5.
66. Bukowski R.M., Stadler W.M., Figlin R.A. et al.: Safety and efficacy of sorafenib in elderly patients (pts) ≥ 65 years: A subset analysis from the Advanced Renal Cell Carcinoma Sorafenib (ARCCS) Expanded Access Program in North America. J. Clin. Oncol. 2008; 26(suppl.): 260s (abstr. 5045).
67. Eisen T., Beck J., Procopio G.: Large open-label, non-comparative phase III study of sorafenib in European pts with advanced RCC (EU-ARCCS): Subgroup analysis of pts with and without baseline clinical cardiovascular diseases (CCD). Ann. Oncol. 2008; 19: viii194-viii195 (abstr. 602P).
68. Llovet J.M., Ricci S., Mazzaferro V. et al.: Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008; 359: 378-390.
69. Schiller J.H., Lee J.W., Hanna N.H. et al.: A randomized discontinuation phase II study of sorafenib versus placebo in patients with non-small cell lung cancer who have failed at least two prior chemotherapy regimens: E2501. J. Clin. Oncol. 2008; 26(suppl.): 427s (abstr. 8014).
70. Escudier B., Eisen T., Stadler W.M. et al.: Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 2007; 356: 125-134.
71. Gollob J.A., Rathmell W.K., Richmond T.M. et al.: Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J. Clin. Oncol. 2007; 25: 3288-3295.
72. Kulke M.H., Lenz H.J., Meropol N.J. et al.: Activity of sunitinib in patients with advanced neuroendocrine tumors. J. Clin. Oncol. 2008; 26: 3403-3410.
73. Porta C., Szczylik C., Bracarda S. et al.: Short and long-term safety with sunitinib in an expanded access trial in metastatic renal cell carcinoma (mRCC). J. Clin. Oncol. 2008; 26(suppl.): 278s (abstr. 5114).
74. Zangari M., Fink L.M., Elice F., Zhan F., Adcock D.M., Tricot G.J.: Thrombotic events in patients with cancer receiving antiangiogenesis agents. J. Clin. Oncol. 2009 Oct 10; 27(29): 4865-73.
75. Wu S., Keresztes R.S.: Antiangiogenic agents for the treatment of nonsmall cell lung cancer: characterizing the molecular basis for serious adverse events. Cancer Invest. 2011 Aug; 29(7): 460-71.
76. Schutz F.A., Je Y., Richards C.J., Choueiri T.K.: Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. J. Clin. Oncol. 2012 Mar 10; 30(8): 871-7.
77. Scagliotti G., Novello S., von Pawel J. et al.: Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J. Clin. Oncol. 2010; 28: 1835-1842.
78. Escudier B., Eisen T., Stadler W.M. et al.: Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cell cancer global evaluation trial. J. Clin. Oncol. 2009; 27: 3312-3318.
79. Hudes G.R., Carducci M.A., Choueiri T.K., Esper P., Jonasch E., Kumar R., Margolin K.A., Michaelson M.D., Motzer R.J., Pili R., Roethke S., Srinivas S.: NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy JNCCN. Journal of the National Comprehensive Cancer Network 2011; 9(Suppl. 1): s1-s30.
2. National Cancer Institute: Common Toxicity Criteria version 3. Online: http://ctep.cancer.gov/protocol development/electronic_applications/docs/ctcaev3.pdf.
3. Yancik R., Wesley M.N., Ries L.A. et al.: Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer 1998; 82: 2123-2134.
4. Yancik R., Wesley M.N., Ries L.A. et al.: Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 2001; 285: 885-892.
5. Anderson B., Sawyer D.B.: Predicting and preventing the cardiotoxicity of cancer therapy. Expert Rev. Cardiovasc. Ther. 2008; 6: 1023-1033.
6. Mulrooney D.A., Yeazel M.W., Kawashima T. et al.: Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 2009; b4606: 339.
7. Yeh E.T., Bickford C.L.: Cardiovascular complications of cancer therapy: incidence, pathogenesis,diagnosis, and management. J. Am. Coll. Cardiol. 2009; 53: 2231-2247.
8. Maitland M.L., Bakris G.L., Black H.R. et al.: Cardiovascular Toxicities Panel, Convened by the Angiogenesis Task Force of the National Cancer Institute Investigational Drug Steering Committee. Initial Assessment, Surveillance, and Management of Blood Pressure in Patients Receiving Vascular Endothelial Growth Factor Signaling Pathway Inhibitors. J. Natl. Cancer Inst. 2010; 102: 596-604.
9. Chu T.F., Rupnick M.A., Kerkela R., Dallabrida S.M., Zurakowski D., Nguyen L. et al.: Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007; 370: 2011-2019.
10. Will Y., Dykens J.A., Nadanaciva S., Hirakawa B., Jamieson J., Marroquin L.D. et al.: Effect of the multitargeted tyrosine kinase inhibitors imatinib, dasatinib, sunitinib, and sorafenib on mitochondrial function in isolated rat heart mitochondria and H9c2 cells. Toxicol. Sci. 2008; 106: 153-161.
11. Gupta R., Maitland M.L.: Sunitinib, hypertension, and heart failure: a model for kinase inhibitor-mediated cardiotoxicity. Curr. Hypertens. Rep. 2011; 13(6): 430-5.
12. Launay-Vacher V., Deray G.: Hypertension and proteinuria: a class-effect of antiangiogenic therapies. Anticancer Drugs 2009 Jan; 20(1): 81-2.
13. Sica D.A.: Angiogenesis inhibitors and hypertension: an emerging issue. J. Clin. Oncol. 2006; 24: 1329-31.
14. Rini B.I., Cohen D.P., Lu D.R., Chen I., Hariharan S., Gore M.E., Figlin R.A., Baum M.S., Motzer R.J.: Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J. Natl. Cancer Inst. 2011 May 4; 103(9): 763-73.
15. Jain L., Sissung T.M., Danesi R. et al.: Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib. J. Exp. Clin. Cancer Res. 2010 Jul 14; 29: 95.
16. Ravaud A., Sire M.: Arterial hypertension and clinical benefit of sunitinib, sorafenib and bevacizumab in first and second-line treatment of metastatic renal cell cancer. Ann. Oncol. 2009; 20(5): 966-7.
17. Szmit S., Langiewicz P., Zołnierek J., Nurzyński P., Zaborowska M., Filipiak K.J., Opolski G., Szczylik C.: Hypertension as a predictive factor for survival outcomes in patients with metastatic renal cell carcinoma treated with sunitinib after progression on cytokines. Kidney Blood Press. Res. 2012; 35(1): 18-25.
18. Rutkowski P., Bylina E., Switaj T. et al.: An analysis of arterial hypertension and mutational status as predictive factors for results of sunitinib (SU) therapy in gastrointestinal stromal tumors (GIST). ASCO Meeting Abstracts 2011; 29(15 Suppl): 10017.
19. Szmit S., Zaborowska M., Waśko-Grabowska A., Zołnierek J., Nurzyński P., Filipiak K.J., Opolski G., Szczylik C.: Cardiovascular Comorbidities for Prediction of Progression-Free Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Sorafenib. Kidney Blood Press. Res. 2012 Jun 6; 35(6): 468-476.
20. Force T., Krause D.S., Van Etten R.A.: Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat. Rev. Cancer 2007; 7: 332-344.
21. Izumiya Y., Shiojima I., Sato K., Sawyer D.B., Colucci W.S., Walsh K.: Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Hypertension 2006; 47: 887-893.
22. Kamba T., Tam B.Y., Hashizume H., Haskell A., Sennino B., Mancuso M.R. et al.: VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am. J. Physiol. Heart Circ. Physiol. 2006; 290: H560-H576.
23. Chintalgattu V., Ai D., Langley R.R. et al.: Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to loadinduced stress. J. Clin. Invest. 2010; 120: 472-484.
24. Kerkela R., Woulfe K.C., Durand J.B. et al.: Sunitinib-induced cardiotoxicity is mediated by offtarget inhibition of AMP-activated protein kinase. Clin. Transl. Sci. 2009; 2: 15-25.
25. Kappers M.H., van Esch J.H., Sleijfer S., Danser A.H., van den Meiracker A.H.: Cardiovascular and renal toxicity during angiogenesis inhibition: clinical and mechanistic aspects. J. Hypertens. 2009 Dec; 27(12): 2297-309.
26. Motzer R.J., Hutson T.E., Tomczak P., Michaelson M.D., Bukowski R.M., Rixe O. et al.: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 2007; 356: 115-124.
27. Motzer R.J., Michaelson M.D., Redman B.G., Hudes G.R., Wilding G., Figlin R.A. et al.: Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 2006; 24: 16-24.
28. Demetri G.D., van Oosterom A.T., Garrett C.R., Blackstein M.E., Shah M.H., Verweij J. et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomized controlled trial. Lancet 2006; 368: 1329-1338.
29. Khakoo A.Y., Kassiotis C.M., Tannir N., Plana J.C., Halushka M., Bickford C. et al.: Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer 2008; 112: 2500-2508.
30. Schmidinger M., Zielinski C.C., Vogl U.M., Bojic A., Bojic M., Schukro C. et al.: Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 2008; 26: 5204-5212.
31. Telli M.L., Witteles R.M., Fisher G.A., Srinivas S.: Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann. Oncol. 2008; 19: 1613-8.
32. Karp J.E., Gojo I., Pili R., Gocke C.D., Greer J., Guo C. et al.: Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-darabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clin. Cancer Res. 2004; 10: 3577-3585.
33. Petrini I., Lencioni M., Ricasoli M., Iannopollo M., Orlandini C., Oliveri F., Bartolozzi C., Ricci S.: Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma. Cancer Chemother. Pharmacol. 2012 Mar; 69(3): 773-80.
34. Toubert M.E., Vercellino L., Faugeron I., Lussato D., Hindie E., Bousquet G.: Fatal heart failure after a 26-month combination of tyrosine kinase inhibitors in a papillary thyroid cancer. Thyroid 2011 Apr; 21(4): 451-4.
35. Tolcher A.W., Appleman L.J., Shapiro G.I., Mita A.C., Cihon F., Mazzu A., Sundaresan P.R.: A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer. Cancer Chemother. Pharmacol. 2011; 67(4): 751-64.
36. Kamada P., Dudek A.Z.: Sorafenib therapy for metastatic renal carcinoma in patients with low cardiac ejection fraction: report of two cases and literature review. Cancer Invest. 2010; 28: 501-4.
37. Wong M.K., Jarkowski A.: Response to sorafenib after sunitinib-induced acute heart failure in a patient with metastatic renal cell carcinoma: case report and review of the literature. Pharmacotherapy 2009; 29: 473-8.
38. Sablin M.P., Bouaita L., Balleguier C., Gautier J., Celier C., Balcaceres J.L. et al.: Sequential use of sorafenib and sunitinib in renal cancer: Retrospective analysis in 90 patients (Abstract). J. Clin. Oncol. 2007; 25(18 Suppl.): 5038.
39. French K.J., Coatney R.W., Renninger J.P., Hu C.X., Gales T.L., Zhao S., Storck L.M., Davis C.B., McSurdy-Freed J., Chen E., Frazier K.S.: Differences in effects on myocardium and mitochondria by angiogenic inhibitors suggest separate mechanisms of cardiotoxicity. Toxicol. Pathol. 2010; 38(5): 691-702.
40. Garcipérez de Vargas F.J., Gómez-Barrado J.J., Ortiz C., Mendoza J., Sánchez-Calderón P., Marcos G.: Refractory heart failure in a patient treated with bevacizumab. Med. Intensiva. 2012. Online .
41. Hawkes E.A., Okines A.F., Plummer C., Cunningham D.: Cardiotoxicity in patients treated with bevacizumab is potentially reversible. J. Clin. Oncol. 2011 Jun 20; 29(18): e560-2.
42. Szmit S., Nurzyński P., Szaluś N., Opolski G., Szczylik C.: Reversible myocardial dysfunction in a young woman with metastatic renal cell carcinoma treated with sunitinib. Acta Oncol. 2009; 48(6): 921-5.
43. Choueiri T.K., Mayer E.L., Je Y., Rosenberg J.E., Nguyen P.L., Azzi G.R., Bellmunt J., Burstein H.J., Schutz F.A.: Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J. Clin. Oncol. 2011 Feb 20; 29(6): 632-8.
44. Richards C.J., Je Y., Schutz F.A., Heng D.Y., Dallabrida S.M., Moslehi J.J., Choueiri T.K.: Incidence and risk of congestive heart failure in patients with renal and nonrenal cell carcinoma treated with sunitinib. J. Clin. Oncol. 2011 Sep 1; 29(25): 3450-6.
45. Ewer M.S., Suter T.M., Lenihan D.J. et al.: Cardiovascular adverse events (CV-AES) in a pooled analysis of 1090 patients (PT) from phase 3 suntinib (SU) trials. Ann. Oncol. 2010; 21(suppl 8): viii166 (abstr. 506P).
46. Khorana A.A., Francis C.W., Culakova E. et al.: Thromboembolism is a leading cause of death in cancer patients receiving chemotherapy. J. Thromb. Haemost. 2007; 5: 632-634.
47. Chew H.K., Wun T., Harvey D., Zhou H., White R.H.: Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch. Intern. Med. 2006 Feb 27; 166(4): 458-64.
48. Prandoni P., Lensing A.W., Piccioli A., Bernardi E., Simioni P., Girolami B., Marchiori A., Sabbion P., Prins M.H., Noventa F., Girolami A.: Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002 Nov 15; 100(10): 3484-8.
49. Alikhan R., Cohen A.T., Combe S., Samama M.M., Desjardins L., Eldor A., Janbon C., Leizorovicz A., Olsson C.G., Turpie A.G.; MEDENOX Study: Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch. Intern. Med. 2004; 164(9): 963-8.
50. Prandoni P.: Cancer and thromboembolic disease: how important is the risk of thrombosis? Cancer Treat. Rev. 2002; 28: 133-136.
51. Fisher B., Costantino J.P., Wickerham D.L., Redmond C.K., Kavanah M., Cronin W.M., Vogel V., Robidoux A., Dimitrov N., Atkins J., Daly M., Wieand S., Tan-Chiu E., Ford L., Wolmark N.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl. Cancer Inst. 1998 Sep 16; 90(18): 1371-88.
52. Saphner T., Tormey D.C., Gray R.: Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. J. Clin. Oncol. 1991; 9(2): 286-94.
53. Blom J.W., Vanderschoot J.P., Oostindiër M.J. et al.: Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J. Thromb. Haemost. 2006; 4: 529-35.
54. Khorana A.A., Francis C.W., Culakova E. et al.: Risk factors for chemotherapy-induced venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-2829.
55. Heit J.A., Silverstein M.D., Mohr D.N. et al.: Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch. Intern. Med. 2000; 160: 809-15.
56. Khorana A.A., Kuderer N.M., Culakova E., Lyman G.H., Francis C.W.: Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111(10): 4902-7.
57. Elice F., Rodeghiero F., Falanga A., Rickles F.R.: Thrombosis associated with angiogenesis inhibitors. Best Pract. Res. Clin. Haematol. 2009; 22: 115--128.
58. Nalluri S.R., Chu D., Keresztes R., Zhu X., Wu S.: Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008; 300: 2277-2285.
59. Scappaticci F.A., Skillings J.R., Holden S.N. et al.: Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J. Natl. Cancer Inst. 2007; 99: 1232-1239.
60. Ranpura V., Hapani S., Chuang J. et al.: Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis in bevacizumab in cancer patients: A meta-analysis of randomized controlled trials. Acta Oncol. 2010; 49: 287-297.
61. Kuenen B.C., Levi M., Meijers J.C., Kakkar A.K., van Hinsbergh V.W., Kostense P.J. et al.: Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1500-1505.
62. Naib T., Steingart R.M., Chen C.L.: Sorafenib-associated multivessel coronary artery vasospasm. Herz. 2011 Jun; 36(4): 348-51.
63. Arima Y., Oshima S., Noda K., Fukushima H., Taniguchi I., Nakamura S., Shono M., Ogawa H.: Sorafenib-induced acute myocardial infarction due to coronary artery spasm. J. Cardiol. 2009 Dec; 54(3): 512-5.
64. Pantaleo M.A., Mandrioli A., Saponara M., Nannini M., Erente G., Lolli C., Biasco G.: Development of coronary artery stenosis in a patient with metastatic renal cell carcinoma treated with sorafenib. BMC Cancer 2012 Jun 11; 12(1): 231.
65. Choueiri T.K., Schutz F.A., Je Y., Rosenberg J.E., Bellmunt J.: Risk of Arterial Thromboembolic Events With Sunitinib and Sorafenib: A Systematic Review and Meta-Analysis of Clinical Trials. J. Clin. Oncol. 2010 May 1; 28(13): 2280-5.
66. Bukowski R.M., Stadler W.M., Figlin R.A. et al.: Safety and efficacy of sorafenib in elderly patients (pts) ≥ 65 years: A subset analysis from the Advanced Renal Cell Carcinoma Sorafenib (ARCCS) Expanded Access Program in North America. J. Clin. Oncol. 2008; 26(suppl.): 260s (abstr. 5045).
67. Eisen T., Beck J., Procopio G.: Large open-label, non-comparative phase III study of sorafenib in European pts with advanced RCC (EU-ARCCS): Subgroup analysis of pts with and without baseline clinical cardiovascular diseases (CCD). Ann. Oncol. 2008; 19: viii194-viii195 (abstr. 602P).
68. Llovet J.M., Ricci S., Mazzaferro V. et al.: Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008; 359: 378-390.
69. Schiller J.H., Lee J.W., Hanna N.H. et al.: A randomized discontinuation phase II study of sorafenib versus placebo in patients with non-small cell lung cancer who have failed at least two prior chemotherapy regimens: E2501. J. Clin. Oncol. 2008; 26(suppl.): 427s (abstr. 8014).
70. Escudier B., Eisen T., Stadler W.M. et al.: Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 2007; 356: 125-134.
71. Gollob J.A., Rathmell W.K., Richmond T.M. et al.: Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J. Clin. Oncol. 2007; 25: 3288-3295.
72. Kulke M.H., Lenz H.J., Meropol N.J. et al.: Activity of sunitinib in patients with advanced neuroendocrine tumors. J. Clin. Oncol. 2008; 26: 3403-3410.
73. Porta C., Szczylik C., Bracarda S. et al.: Short and long-term safety with sunitinib in an expanded access trial in metastatic renal cell carcinoma (mRCC). J. Clin. Oncol. 2008; 26(suppl.): 278s (abstr. 5114).
74. Zangari M., Fink L.M., Elice F., Zhan F., Adcock D.M., Tricot G.J.: Thrombotic events in patients with cancer receiving antiangiogenesis agents. J. Clin. Oncol. 2009 Oct 10; 27(29): 4865-73.
75. Wu S., Keresztes R.S.: Antiangiogenic agents for the treatment of nonsmall cell lung cancer: characterizing the molecular basis for serious adverse events. Cancer Invest. 2011 Aug; 29(7): 460-71.
76. Schutz F.A., Je Y., Richards C.J., Choueiri T.K.: Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. J. Clin. Oncol. 2012 Mar 10; 30(8): 871-7.
77. Scagliotti G., Novello S., von Pawel J. et al.: Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J. Clin. Oncol. 2010; 28: 1835-1842.
78. Escudier B., Eisen T., Stadler W.M. et al.: Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cell cancer global evaluation trial. J. Clin. Oncol. 2009; 27: 3312-3318.
79. Hudes G.R., Carducci M.A., Choueiri T.K., Esper P., Jonasch E., Kumar R., Margolin K.A., Michaelson M.D., Motzer R.J., Pili R., Roethke S., Srinivas S.: NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy JNCCN. Journal of the National Comprehensive Cancer Network 2011; 9(Suppl. 1): s1-s30.