Conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting tyrosine kinase inhibitor-based therapy

Expert Opinion on Drug Safety

Volumn 14, Issue 2, 2015, Pages 253-267

  Bronte, Giuseppe ^a   Bronte, Enrico ^a   Novo, Giuseppina ^b   Pernice, Gianfranco ^a   Lo Vullo, Francesca ^a   Musso, Emmanuela ^a   Bronte, Fabrizio ^b   Gulotta, Eliana ^a   Rizzo, Sergio ^a   Rolfo, Christian ^c   Silvestris, Nicola ^d   Bazan, Viviana ^a   Novo, Salvatore ^b   Russo, Antonio ^a  

^a UNIVERSITY OF PALERMO   (Italy)

^b UNIVERSITY OF PALERMO   (Italy)

^c UNIVERSITY OF ANTWERP   (Belgium)

^d NATIONAL CANCER INSTITUTE GIOVANNI PAOLO II   (Italy)

Author keywords

Axitinib; Cardio oncology; Cardiotoxicity; Pazopanib; Regorafenib; Sorafenib; Sunitinib; Tyrosine kinase inhibitors; Vandetanib; VEGF

Indexed keywords

ANGIOGENESIS INHIBITOR; AXITINIB; NINTEDANIB; PAZOPANIB; PROTEIN TYROSINE KINASE INHIBITOR; REGORAFENIB; SORAFENIB; SUNITINIB; VANDETANIB; VATALANIB; ANTINEOPLASTIC AGENT; NEW DRUG; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; VASCULOTROPIN RECEPTOR;

ASTHENIA; CANCER CHEMOTHERAPY; CANCER PATIENT; CARDIOLOGIST; CARDIOTOXICITY; CONGESTIVE HEART FAILURE; DRUG EFFICACY; DYSPNEA; HEALTH STATUS; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HUMAN; HYPERTENSION; ONCOLOGIST; PATHOPHYSIOLOGY; QT PROLONGATION; REVIEW; THROMBOEMBOLISM; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; CARDIOVASCULAR DISEASE; CHEMICALLY INDUCED; DRUG EFFECTS; HEART; MOLECULARLY TARGETED THERAPY; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; VASCULARIZATION;

ANTINEOPLASTIC AGENTS; CARDIOVASCULAR DISEASES; DRUGS, INVESTIGATIONAL; HEART; HUMANS; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR;

EID: 84921405856     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2015.986092     Document Type: Review

References (91)

1. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature 2005;438(7070):967-74
2. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9(6):669-76
3. Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer 2013;13(12):871-82
4. Caraglia M, Santini D, Bronte G, et al. Predicting efficacy and toxicity in the era of targeted therapy: focus on anti-EGFR and anti-VEGF molecules. Curr Drug Metab 2011;12(10):944-55
5. Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol 2010;28(6):1075-83
6. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008;8(8):579-91
7. Liu S, Kurzrock R. Toxicity of targeted therapy: implications for response and impact of genetic polymorphisms. Cancer Treat Rev 2014;40(7):883-91
8. Liebler DC, Guengerich FP. Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discov 2005;4(5):410-20
9. Orphanos GS, Ioannidis GN, Ardavanis AG. Cardiotoxicity induced by tyrosine kinase inhibitors. Acta Oncol 2009;48(7):964-70
10. Cheng H, Force T. Why do kinase inhibitors cause cardiotoxicity and what can be done about it? Prog Cardiovasc Dis 2010;53(2):114-20
11. Hasinoff BB. The cardiotoxicity and myocyte damage caused by small molecule anticancer tyrosine kinase inhibitors is correlated with lack of target specificity. Toxicol Appl Pharmacol 2010;244(2):190-5
12. Fabian MA, Biggs WH, Treiber DK, et al. A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 2005;23(3):329-36
13. Kerkela R, Woulfe KC, Durand JB, et al. Sunitinib-induced cardiotoxicity is mediated by off-target inhibition of AMP-activated protein kinase. Clin Transl Sci 2009;2(1):15-25
14. Hasinoff BB, Patel D, O'Hara KA. Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine kinase inhibitor sunitinib. Mol Pharmacol 2008;74(6):1722-8
15. Vaklavas C, Lenihan D, Kurzrock R, Tsimberidou AM. Anti-vascular endothelial growth factor therapies and cardiovascular toxicity: what are the important clinical markers to target? Oncologist 2010;15(2):130-41
16. Gupta R, Maitland ML. Sunitinib, hypertension, and heart failure: a model for kinase inhibitor-mediated cardiotoxicity. Curr Hypertens Rep 2011;13(6):430-5
17. Henry TD, Annex BH, McKendall GR, et al. The VIVA trial: vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation 2003;107(10):1359-65
18. Felmeden DC, Spencer CG, Belgore FM, et al. Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management. Am J Hypertens 2003;16(1):11-20
19. Giordano FJ, Gerber HP, Williams SP, et al. A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci USA 2001;98(10):5780-5
20. Chintalgattu V, Ai D, Langley RR, et al. Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress. J Clin Invest 2010;120(2):472-84
21. Taimeh Z, Loughran J, Birks EJ, Bolli R. Vascular endothelial growth factor in heart failure. Nat Rev Cardiol 2013;10(9):519-30
22. Tao Z, Chen B, Tan X, et al. Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart. Proc Natl Acad Sci USA 2011;108(5):2064-9
23. Kappers MH, de Beer VJ, Zhou Z, et al. Sunitinib-induced systemic vasoconstriction in swine is endothelin mediated and does not involve nitric oxide or oxidative stress. Hypertension 2012;59(1):151-7
24. Chintalgattu V, Rees ML, Culver JC, et al. Coronary microvascular pericytes are the cellular target of sunitinib malate-induced cardiotoxicity. Sci Transl Med 2013;5(187):187ra69
25. Nachman RL, Rafii S. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med 2008;359(12):1261-70
26. Möhle R, Green D, Moore MA, et al. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci USA 1997;94(2):663-8
27. Carmeliet P, Lampugnani MG, Moons L, et al. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 1999;98(2):147-57
28. Lampugnani MG, Orsenigo F, Gagliani MC, et al. Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J Cell Biol 2006;174(4):593-604
29. Shay-Salit A, Shushy M, Wolfovitz E, et al. VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells. Proc Natl Acad Sci U SA 2002;99(14):9462-7
30. Lee S, Chen TT, Barber CL, et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell 2007;130(4):691-703
31. Hasinoff BB, Patel D. Mechanisms of myocyte cytotoxicity induced by the multikinase inhibitor sorafenib. Cardiovasc Toxicol 2010;10(1):1-8
32. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378-90
33. Bronte F, Bronte G, Cusenza S, et al. Targeted therapies in hepatocellular carcinoma. Curr Med Chem 2014;21(8):966-74
34. Escudier B, Eisen T, Stadler WM, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 2009;27(20):3312-18
35. Stadler WM, Figlin RA, McDermott DF, et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 2010;116(5):1272-80
36. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10(1):25-34
37. 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; author reply 67
38. Choueiri TK, Schutz FA, Je Y, et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol 2010;28(13):2280-5
39. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368(9544):1329-38
40. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115-24
41. Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011;364(6):501-13
42. Chen MH, Kerkelä R, Force T. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation 2008;118(1):84-95
43. Rini BI, Cohen DP, LU DR, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 2011;103(9):763-73
44. Chu TF, Rupnick MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007;370(9604):2011-19
45. Schmidinger M, Zielinski CC, Vogl UM, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2008;26(32):5204-12
46. Hutson TE, Davis ID, Machiels JP, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 2010;28(3):475-80
47. Davidson BA, Secord AA. Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer. Int J Womens Health 2014;6:289-300
48. Qi WX, Lin F, Sun YJ, et al. Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis. Cancer Chemother Pharmacol 2013;71(2):431-9
49. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28(6):1061-8
50. Pick AM, Nystrom KK. Pazopanib for the treatment of metastatic renal cell carcinoma. Clin Ther 2012;34(3):511-20
51. van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012;379(9829):1879-86
52. Macy ME, DeRyckere D, Gore L. Vandetanib mediates anti-leukemia activity by multiple mechanisms and interacts synergistically with DNA damaging agents. Invest New Drugs 2012;30(2):468-79
53. Grande E, Kreissl MC, Filetti S, et al. Vandetanib in advanced medullary thyroid cancer: review of adverse event management strategies. Adv Ther 2013;30(11):945-66
54. Holden SN, Eckhardt SG, Basser R, et al. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol 2005;16(8):1391-7
55. Force T, Krause DS, Van Etten RA. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer 2007;7(5):332-44
56. Tamura T, Minami H, Yamada Y, et al. A phase I dose-escalation study of ZD6474 in Japanese patients with solid, malignant tumors. J Thorac Oncol 2006;1(9):1002-9
57. Wells SA, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012;30(2):134-41
58. Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol 2012;13(9):897-905
59. Qi WX, Shen Z, Lin F, et al. Incidence and risk of hypertension with vandetanib in cancer patients: a systematic review and meta-analysis of clinical trials. Br J Clin Pharmacol 2013;75(4):919-30
60. Zang J, Wu S, Tang L, et al. Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis. PLoS One 2012;7(2):e30353
61. Verzoni E, Grassi P, Testa I, et al. Targeted treatments in advanced renal cell carcinoma: focus on axitinib. Pharmgenomics Pers Med 2014;7:107-16
62. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011;378(9807):1931-9
63. Rini BI, Schiller JH, Fruehauf JP, et al. Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors. Clin Cancer Res 2011;17(11):3841-9
64. Qi WX, He AN, Shen Z, Yao Y. Incidence and risk of hypertension with a novel multi-targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta-analysis. Br J Clin Pharmacol 2013;76(3):348-57
65. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol 2013;14(13):1287-94
66. Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011;129(1):245-55
67. FDA approves regorafenib (Stivarga) for GIST. Oncology (Williston Park) 2013;27(3):164
68. FDA approves regorafenib (Stivarga) for metastatic colorectal cancer. Oncology (Williston Park) 2012;26(10):896
69. Rolfo C, Bronte G, Sortino G, et al. The role of targeted therapy for gastrointestinal tumors. Expert Rev Gastroenterol Hepatol 2014;8(8):875-85
70. Demetri GD, Reichardt P, Kang YK, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381(9863):295-302
71. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381(9863):303-12
72. Bronte G, Rolfo C, Peeters M, Russo A. How to find the Ariadne's thread in the labyrinth of salvage treatment options for metastatic colorectal cancer? Expert Opin Biol Ther 2014;14(6):743-8
73. Kerbel RS. Antiangiogenic therapy: a universal chemosensitization strategy for cancer? Science 2006;312(5777):1171-5
74. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 2000;60(8):2178-89
75. Hecht JR, Trarbach T, Hainsworth JD, et al. Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J Clin Oncol 2011;29(15):1997-2003
76. Van Cutsem E, Bajetta E, Valle J, et al. Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol 2011;29(15):2004-10
77. Gauler TC, Besse B, Mauguen A, et al. Phase II trial of PTK787/ZK 222584 (vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or progressing patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). Ann Oncol 2012;23(3):678-87
78. Dragovich T, Laheru D, Dayyani F, et al. Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). Cancer Chemother Pharmacol 2014;74(2):379-87
79. Eisen T, Shparyk Y, Macleod N, et al. Effect of small angiokinase inhibitor nintedanib (BIBF 1120) on QT interval in patients with previously untreated, advanced renal cell cancer in an open-label, phase II study. Invest New Drugs 2013;31(5):1283-93
80. Rolfo C, Raez LE, Bronte G, et al. BIBF 1120/nintedanib: a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer. Expert Opin Investig Drugs 2013;22(8):1081-8
81. Doebele RC, Conkling P, Traynor AM, et al. A phase I, open-label dose-escalation study of continuous treatment with BIBF 1120 in combination with paclitaxel and carboplatin as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol 2012;23(8):2094-102
82. Ledermann JA, Hackshaw A, Kaye S, et al. Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol 2011;29(28):3798-804
83. Reck M, Kaiser R, Mellemgaard A, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 2014;15(2):143-55
84. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335-42
85. Abdel-Rahman O, Fouad M. Bevacizumab-based combination therapy for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a systematic review of the literature. J Cancer Res Clin Oncol 2014. In press
86. Kümler I, Christiansen OG, Nielsen DL. A systematic review of bevacizumab efficacy in breast cancer. Cancer Treat Rev 2014;40(8):960-73
87. Xia Y, Song X, Li D, et al. YLT192, a novel, orally active bioavailable inhibitor of VEGFR2 signaling with potent antiangiogenic activity and antitumor efficacy in preclinical models. Sci Rep 2014;4:6031
88. Tian S, Quan H, Xie C, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci 2011;102(7):1374-80
89. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014;383(9911):31-9
90. Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014;15(11):1224-35
91. Bronte G, Galvano A, Cicero G, et al. Ramucirumab and its use in gastric cancer treatment. Drugs Today (Barc) 2014;50(9):613-21