Cardiovascular complications associated with novel angiogenesis inhibitors: Emerging evidence and evolving perspectives

Trends in Cardiovascular Medicine

Volumn 23, Issue 4, 2013, Pages 104-113

  Bair, Steven M ^a,b   Choueiri, Toni K ^b   Moslehi, Javid ^a,b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AFLIBERCEPT; ANGIOGENESIS INHIBITOR; AXITINIB; BEVACIZUMAB; BRIVANIB; CABOZANTINIB; CEDIRANIB; PAZOPANIB; RAMUCIRUMAB; REGORAFENIB; SEMAXANIB; SORAFENIB; SUNITINIB; TIVOZANIB; VANDETANIB;

ADVANCED CANCER; ARTERIAL THROMBOEMBOLISM; BLOOD PRESSURE MONITORING; CANCER CHEMOTHERAPY; CANCER PATIENT; CARDIOLOGIST; CARDIOMYOPATHY; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; COLORECTAL CANCER; CONGESTIVE HEART FAILURE; DISEASE ASSOCIATION; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL STROMAL TUMOR; GLIOBLASTOMA; HEART LEFT VENTRICLE FAILURE; HUMAN; HYPERTENSION; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; PRIORITY JOURNAL; PROSPECTIVE STUDY; REVIEW; SIGNAL TRANSDUCTION; SOFT TISSUE SARCOMA; THYROID MEDULLARY CARCINOMA; VENOUS THROMBOEMBOLISM;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; CARDIOTOXINS; CARDIOVASCULAR DISEASES; HUMANS; MEDICATION THERAPY MANAGEMENT; NEOVASCULARIZATION, PATHOLOGIC; PATIENT CARE TEAM; SIGNAL TRANSDUCTION; TRANSLATIONAL MEDICAL RESEARCH; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84875886935     PISSN: 10501738     EISSN: 18732615     Source Type: Journal    
DOI: 10.1016/j.tcm.2012.09.008     Document Type: Review

References (65)

1. Alon T., Hemo I., Itin A., Pe'er J., Stone J., Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nature Medicine 1995, 1:1024-1028.
2. Azizi M., Chedid A., Oudard S. Home blood-pressure monitoring in patients receiving sunitinib. New England Journal of Medicine 2008, 358:95-97.
3. Baffert F., Le T., Sennino B., Thurston G., Kuo C.J., Hu-Lowe D., et al. Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. American Journal of Physiology: Heart and Circulatory Physiology 2006, 290:H547-H559.
4. Camera M., Giesen P.L., Fallon J., Aufiero B.M., Taubman M., Tremoli E., et al. Cooperation between VEGF and TNF-alpha is necessary for exposure of active tissue factor on the surface of human endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology 1999, 19:531-537.
5. Chintalgattu V., Ai D., Langley R.R., Zhang J., Bankson J.A., Shih T.L., et al. Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress. Journal of Clinical Investigation 2010, 120:472-484.
6. Choueiri T.K., Schutz F.A.B., Je Y., Rosenberg J.E., Bellmont J. Risk of arterial thromboembolic events with sunitinb and sorafenib: a systematic review and meta-analysis of clinical trials. Journal of Clinical Oncology 2010, 28:2280-2285.
7. Choueiri T.K., Mayer E.L., Je Y., Rosenberg J.E., Nguyen P.L., Azzi G.R., et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. Journal of Clinical Oncology 2011, 29:632-638.
8. 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.
9. Dienstmann R., Ades F., Saini K.S., Metzger-Filho O. Benefit-risk assessment of bevacizumab in breast cancer. Drug Safety 2012, 35:15-25.
10. Dimmeler S., Fleming I., Fisslthaler B., Hermann C., Busse R., Zeiher A.M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999, 399:601-605.
11. Facemire C.S., Nixon A.B., Griffiths R., Hurwitz H., Coffman T.M. Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide synthase expression. Hypertension 2009, 54:652-658.
12. Folkman J., Merler E., Abernathy C., Williams G. Isolation of a tumor factor responsible for angiogenesis. Journal of Experimental Medicine 1971, 133:275-288.
13. Force T., Kerkela R. Cardiotoxicity of the new cancer therapeutics-mechanisms of, and approaches to, the problem. Drug Discovery Today 2008, 13:778-784.
14. Fulton D., Gratton J.P., McCabe T.J., Fontana J., Fujio Y., Walsh K., et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999, 399:597-601.
15. Geiger-Gritsch S., Stollenwerk B., Miksad R., Guba B., Wild C., Siebert U. Safety of bevacizumab in patients with advanced cancer: a meta-analysis of randomized controlled trials. Oncologist 2010, 15:1179-1191.
16. Gerber H.P., McMurtrey A., Kowalski J., Yan M., Keyt B.A., Dixit V., et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. Journal of Biological Chemistry 1998, 273:30336-30343.
17. Gitay-Goren H., Soker S., Vlodavsky I., Neufeld G. The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules. Journal of Biological Chemistry 1992, 267:6093-6098.
18. Hang X.F., Xu W.S., Wang J.X., Wang L., Xin H.G., Zhang R.Q., et al. Risk of high-grade bleeding in patients with cancer treated with bevacizumab: a meta-analysis of randomized controlled trials. European Journal of Clinical Pharmacology 2011, 67:613-623.
19. Hapani S., Sher A., Chu D., Wu S. Increased risk of serious hemorrhage with bevacizumab in cancer patients: a meta-analysis. Oncology 2010, 79:27-38.
20. He H., Venema V.J., Gu X., Venema R.C., Marrero M.B., Caldwell R.B. Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. Journal of Biological Chemistry 1999, 274:25130-25135.
21. Horowitz J.R., Rivard A., van der Zee R., Hariawala M., Sheriff D.D., Esakof D.D., et al. Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Evidence for a maintenance role in quiescent adult endothelium. Arteriosclerosis, Thrombosis, and Vascular Biology 1997, 17:2793-2800.
22. Hurwitz H., Fehrenbacher L., Novotny W., Cartwright T., Hainsworth J., Heim W., et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New England Journal of Medicine 2004, 350:2335-2342.
23. Hurwitz H.I., Saltz L.B., Van Cutsem E., Cassidy J., Wiedemann J., Sirzen F., et al. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. Journal of Clinical Oncology 2011, 29:1757-1764.
24. Ito N., Claesson-Welsh L. Dual effects of heparin on VEGF binding to VEGF receptor-1 and transduction of biological responses. Angiogenesis 1999, 3:159-166.
25. Je Y., Schutz F.A.B., Choueiri T.K. Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Lancet Oncology 2009, 10:967-974.
26. Jin Z.-G., Ueba H., Tanimoto T., Lungu A.O., Frame M.D., Berk B.C. Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase. Circulation Research 2003, 93:354-363.
27. Kappers M.H.W., de Beer V.J., Zhou Z., Danser A.H.J., Sleijfer S., Duncker D.J., et al. Sunitinib-induced systemic vasoconstriction in swine is endothelin mediated and does not involve nitric oxide or oxidative stress. Hypertension 2012, 59:151-157.
28. Kappers M.H.W., Smedts F.M.M., Horn T., van Esch J.H.M., Sleijfer S., Leijten F., et al. The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system. Hypertension 2011, 58:295-302.
29. Kappers M.H.W., van Esch J.H.M., Sluiter W., Sleijfer S., Danser A.H.J., van den Meiracker A.H. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension 2010, 56:675-681.
30. Keck P.J., Hauser S.D., Krivi G., Sanzo K., Warren T., Feder J., et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989, 246:1309-1312.
31. Kerkela R., Woulfe K.C., Durand J.-B., Vagnozzi R., Kramer D., Chu T.F., et al. Sunitinib-induced cardiotoxicity is mediated by off-target inhibition of AMP-activated protein kinase. Clinical and Translational Science 2009, 2:15-25.
32. Leung D.W., Cachianes G., Kuang W.J., Goeddel D.V., Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246:1306-1309.
33. Maitland M.L., Kasza K.E., Karrison T., Moshier K., Sit L., Black H.R., et al. Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment. Clinical Cancer Research 2009, 15:6250-6257.
34. Maitland M.L., Bakris G.L., Black H.R., Chen H.X., Durand J.-B., Elliott W.J., et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. Journal of the National Cancer Institute 2010, 102:596-604.
35. May D., Gilon D., Djonov V., Itin A., Lazarus A., Gordon O., et al. Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation. Proceedings of the National Academy of Sciences 2008, 105:282-287.
36. Mayer E.L., Dallabrida S.M., Rupnick M.A., Redline W.M., Hannagan K., Ismail N.S., et al. Contrary effects of the receptor tyrosine kinase inhibitor vandetanib on constitutive and flow-stimulated nitric oxide elaboration in humans. Hypertension 2011, 58:85-92.
37. Maynard S.E., Min J.-Y., Merchan J., Lim K.-H., Li J., Mondal S., et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. Journal of Clinical Investigation 2003, 111:649-658.
38. Meyer T., Robles-Carrillo L., Robson T., Langer F., Desai H., Davila M., et al. Bevacizumab immune complexes activate platelets and induce thrombosis in FCGR2A transgenic mice. Journal of Thrombosis and Haemostasis 2009, 7:171-181.
39. Mourad J.-J., des Guetz G., Debbabi H., Levy B.I. Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Annals of Oncology 2008, 19:927-934.
40. 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: The journal of the American Medical Association 2008, 300:2277-2285.
41. Nazer B., Humphreys B.D., Moslehi J. Effects of novel angiogenesis inhibitors for the treatment of cancer on the cardiovascular system: focus on hypertension. Circulation 2011, 124:1687-1691.
42. Österlund P., Soveri L.-M., Isoniemi H., Poussa T., Alanko T., Bono P. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy. British Journal of Cancer 2011, 104:599-604.
43. Pepper M.S., Ferrara N., Orci L., Montesano R. Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. Biochemical and Biophysical Research Communications 1991, 181:902-906.
44. Ranpura V., Hapani S., Chuang J., Wu S. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncologica 2010, 49:287-297.
45. Ranpura V., Hapani S., Wu S. Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA: The Journal of the American Medical Association 2011, 305:487-494.
46. Richards C.J., Je Y., Schutz F.A.B., Heng D.Y., Dallabrida S.M., Moslehi J.J., et al. Incidence and risk of congestive heart failure in patients with renal and non-renal cell carcinoma treated with sunitinib. Journal of Clinical Oncology 2011, 29:3450-3456.
47. Robinson E.S., Khankin E.V., Karumanchi S.A., Humphreys B.D. Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker. Seminars in Nephrology 2010, 30:591-601.
48. Robinson E.S., Khankin E.V., Choueiri T.K., Dhawan M.S., Rogers M.J., Karumanchi S.A., et al. Suppression of the nitric oxide pathway in metastatic renal cell carcinoma patients receiving vascular endothelial growth factor-signaling inhibitors. Hypertension 2010, 56:1131-1136.
49. Scappaticci F.A., Skillings J.R., Holden S.N., Gerber H.-P., Miller K., Kabbinavar F., et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. Journal of the National Cancer Institute 2007, 99:1232-1239.
50. 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. Journal of Clinical Oncology 2008, 26:5204-5212.
51. Schutz F.A.B., Je Y., Azzi G.R., Nguyen P.L., Choueiri T.K. Bevacizumab increases the risk of arterial ischemia: a large study in cancer patients with a focus on different subgroup outcomes. Annals of Oncology 2011, 22:1404-1412.
52. Schutz F.A.B., 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. Journal of Clinical Oncology 2012, 30:871-877.
53. Senger D.R., Galli S.J., Dvorak A.M., Perruzzi C.A., Harvey V.S., Dvorak H.F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983, 219:983-985.
54. Sherwood L.M., Parris E.E., Folkman J. Tumor angiogenesis: therapeutic implications. New England Journal of Medicine 1971, 285:1182-1186.
55. Steeghs N., Gelderblom H., Roodt J.O., Christensen O., Rajagopalan P., Hovens M., et al. Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. Clinical Cancer Research 2008, 14:3470-3476.
56. Steeghs N., Rabelink T.J., op 't Roodt J., Batman E., Cluitmans F.H.M., Weijl N.I., et al. Reversibility of capillary density after discontinuation of bevacizumab treatment. Annals of Oncology 2010, 21:1100-1105.
57. Tebbutt N.C., Murphy F., Zannino D., Wilson K., Cummins M.M., Abdi E., et al. Risk of arterial thromboembolic events in patients with advanced colorectal cancer receiving bevacizumab. Annals of Oncology 2011, 22:1834-1838.
58. Tran J., Rak J., Sheehan C., Saibil S.D., LaCasse E., Korneluk R.G., et al. Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. Biochemical and Biophysical Research Communications 1999, 264:781-788.
59. Tsurumi Y., Murohara T., Krasinski K., Chen D., Witzenbichler B., Kearney M., et al. Reciprocal relation between VEGF and NO in the regulation of endothelial integrity. Nature Medicine 1997, 3:879-886.
60. Uraizee I., Cheng S., Moslehi J. Reversible cardiomyopathy associated with sunitinib and sorafenib. New England Journal of Medicine 2011, 365:1649-1650.
61. van der Zee R., Murohara T., Luo Z., Zollmann F., Passeri J., Lekutat C., et al. Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation 1997, 95:1030-1037.
62. Wheeler-Jones C., Abu-Ghazaleh R., Cospedal R., Houliston R.A., Martin J., Zachary I. Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen-activated protein kinase. FEBS Letters 1997, 420:28-32.
63. Witteles R.M., Telli M. Underestimating cardiac toxicity in cancer trials: lessons learned?. Journal of Clinical Oncology 2012, 30:1916-1918.
64. Wu S., Chen J.J., Kudelka A., Lu J., Zhu X. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncology 2008, 9:117-123.
65. Zhu X., Stergiopoulos K., Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncologica 2009, 48:9-17.