Beyond bevacizumab: New anti-VEGF strategies in colorectal cancer

Expert Opinion on Investigational Drugs

Volumn 21, Issue 7, 2012, Pages 949-959

  Troiani, Teresa ^a   Martinelli, Erika ^a   Orditura, Michele ^a   De Vita, Ferdinando ^a   Ciardiello, Fortunato ^a   Morgillo, Floriana ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

Aflibercept; Angiogenesis; Anti VEGF inhibitors; Colorectal cancer; Regorafenib; Targeted therapy

Indexed keywords

AFLIBERCEPT; AZ 2171; BEVACIZUMAB; BRIVANIB; CAPECITABINE PLUS OXALIPLATIN; CEDIRANIB; CETUXIMAB; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; OXALIPLATIN; PANITUMUMAB; RAMUCIRUMAB; REGORAFENIB; SEMAXANIB; SUNITINIB; THROMBOSPONDIN 1; UNCLASSIFIED DRUG; VASCULOTROPIN; VASCULOTROPIN A; VASCULOTROPIN B; VASCULOTROPIN C; VASCULOTROPIN D; VASCULOTROPIN E; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3; VATALANIB;

ADVANCED CANCER; ANGIOGENESIS; ANOREXIA; BINDING AFFINITY; CANCER GROWTH; CARDIOVASCULAR DISEASE; CELL DIFFERENTIATION; CELL MIGRATION; COLORECTAL CANCER; DEHYDRATION; DIARRHEA; DIGESTIVE SYSTEM CANCER; DRUG WITHDRAWAL; FATIGUE; GENE MUTATION; HAND FOOT SYNDROME; HUMAN; HYPERTENSION; KIDNEY CARCINOMA; LOADING DRUG DOSE; LUNG NON SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; METASTASIS; MOLECULAR DIAGNOSIS; MOLECULARLY TARGETED THERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NAUSEA AND VOMITING; NEUTROPENIA; ONCOGENE K RAS; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEINURIA; RASH; RECTUM ULCER; REVIEW; SEPSIS; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; TUMOR RECURRENCE; VOMITING;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL, HUMANIZED; CLINICAL TRIALS AS TOPIC; COLORECTAL NEOPLASMS; DISEASE-FREE SURVIVAL; HUMANS; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84862301209     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2012.689287     Document Type: Review

References (81)

1. Siegel R, Ward E, Brawley O, et al. Cancer statistics. CA Cancer J Clin 2011;61:212-36
2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90
3. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42. (Pubitemid 38702844)
4. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182-6
5. Chu E. An update on the current and emerging targeted agents in metastatic colorectal cancer. Clin Colorectal Cancer 2012;11:1-13
6. Wagner AD, Arnold D, Grothey AA, et al. Anti-angiogenic therapies for metastatic colorectal cancer. Cochrane Database Syst Rev 2009;CD005392
7. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003;3:401-10 (Pubitemid 37328844)
8. Salmon JS, Lockhart AC, Berlin J. Anti-angiogenic treatment of gastrointestinal malignancies. Cancer Invest 2005;23:712-26 (Pubitemid 43041717)
9. Paavonen K, Puolakkainen P, Jussila L, et al. Vascular endothelial growth factor receptor-3 in lymphangiogenesis in wound healing. Am J Pathol 2000;156:1499-504 (Pubitemid 30646689)
10. Terman BI, Dougher-Vermazen M, Carrion ME, et al. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 1992;187:1579-86
11. Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998;92:735-45 (Pubitemid 28155313)
12. Fong GH, Rossant J, Gertsenstein M, et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995;376:66-70
13. Hiratsuka S, Maru Y, Okada A, et al. Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res 2001;61:1207-13 (Pubitemid 32174444)
14. Fan F, Wey JS, McCarty MF, et al. Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells. Oncogene 2005;24:2647-53 (Pubitemid 40593092)
15. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002;20:4368-80 (Pubitemid 35266299)
16. Zeng H, Dvorak HF, Mukhopadhyay D. Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) receptor-1 down-modulates VPF/VEGF receptor-2-mediated endothelial cell proliferation, but not migration, through phosphatidylinositol 3-kinase-dependent pathways. J Biol Chem 2001;276:26969-79
17. Millauer B, Wizigmann-Voos S, Schnurch H, et al. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 1993;72:835-46 (Pubitemid 23110226)
18. Kaipainen A, Korhonen J, Mustonen T, et al. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci USA 1995;92:3566-70
19. Mandriota SJ, Jussila L, Jeltsch M, et al. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 2001;20:672-82 (Pubitemid 32167632)
20. Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med 2001;7:186-91 (Pubitemid 32148485)
21. Takahashi Y, Tucker SL, Kitadai Y, et al. Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. Arch Surg 1997;132:541-6 (Pubitemid 27215097)
22. Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 1995;55:3964-8
23. Saltz LB, Clarcke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26:2013-19
24. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007;25:1539-44. (Pubitemid 46733080)
25. Cascinu S, Staccioli MP, Gasparini G, et al. Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer. Clin Cancer Res 2000;6:2803-7 (Pubitemid 30482120)
26. Cascone T, Herynk MH, Xu L, et al. Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. J Clin Invest 2011;121(4):1313-28
27. Kuboki Y, Yoshino T, Yamazaki K, et al. A multicenter, randomized, double-blind, phase II study of TAS-102 plus best supportive care (BSC) versus Placebo plus BSC in patients with chemotherapy-refractory metastatic colorectal cancer (10040030 study). ESMO 2011;16:abstract 6005
28. Chu QS. Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors. Expert Opin Biol Ther 2009;9:263-71
29. Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 2002;99:11393-8 (Pubitemid 34920936)
30. Fukasawa M, Korc M. Vascular endothelial growth factor-trap suppresses tumorigenicity of multiple pancreatic cancer cell lines. Clin Cancer Res 2004;10:3327-32 (Pubitemid 38685437)
31. Kadenhe-Chiweshe A, Papa J, McCrudden KW, et al. Sustained VEGF blockade results in microenvironmental sequestration of VEGF by tumors and persistent VEGF receptor-2 activation. Mol Cancer Res 2008;6:1-9 (Pubitemid 351378161)
32. Lockhart AC, Rothenberg ML, Dupont J, et al. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol 2010;28:207-14
33. Tang P, Cohen SJ, Bjarnason GA, et al. Phase II trial of aflibercept (VEGF Trap) in previously treated patients with metastatic colorectal cancer (MCRC): a PMH phase II consortium trial. J Clin Oncol 2008;26(Suppl 26): abstract 4027
34. Van Cutsem E, Tabernero J, Lakomy R, et al. Intravenous aflibercept versus placebo in combination with irinotecan/5-FU (FOLFIRI) for second-line treatment of metastatic colorectal cancer (MCRC): results of a multinational Phase III trial (EFC10262-VELOUR). Ann Oncol 2011;22:22.
35. Prewett M, Huber J, Li Y, et al. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 1999;59:5209-18 (Pubitemid 29503984)
36. Spratlin JL, Mulder KE, Mackey JR. Ramucirumab (IMC-1121B): a novel attack on angiogenesis. Future Oncol 2010;6:1085-94
37. Spratlin JL, Cohen RB, Eadens M, et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 2010;28:780-7
38. A study in second line metastatic colorectal cancer. Available from: http://clinicaltrials.gov/ct2/results? term-NCT01183780 [Accessed 13 December 2010]
39. Garcia-Carbonero R, Rivera F, Maurel J, et al. A phase II, open-label study evaluating the safety and efficacy of ramucirumab combined with (mFOLFOX6) as first line therapy in patients with metastatic colorectal cancer [abstract 533]. ASCO Gastrointestinal cancer symposium; 2012
40. O'Farrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003;101:3597-605 (Pubitemid 36857948)
41. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9:327-37 (Pubitemid 36109749)
42. Castillo-Avila W, Piulats JM, Garcia Del Muro X, et al. Sunitinib inhibits tumor growth and synergizes with cisplatin in orthotopic models of cisplatin-sensitive and cisplatin-resistant human testicular germ cell tumors. Clin Cancer Res 2009;15:3384-95
43. Cumashi A, Tinari N, Rossi C, et al. Sunitinib malate (SU-11248) alone or in combination with low-dose docetaxel inhibits the growth of DU-145 prostate cancer xenografts. Cancer Lett 2008;270:229-33
44. Krystal GW, Honsawek S, Kiewlich D, et al. Indolinone tyrosine kinase inhibitors block Kit activation and growth of small cell lung cancer cells. Cancer Res 2001;61:3660-8 (Pubitemid 32694977)
45. Marzola P, Degrassi A, Calderan L, et al. Early antiangiogenic activity of SU11248 evaluated in vivo by dynamic contrast-enhanced magnetic resonance imaging in an experimental model of colon carcinoma. Clin Cancer Res 2005;11:5827-32 (Pubitemid 41170309)
46. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 2006;24:25-35 (Pubitemid 46630490)
47. Saltz LB, Rosen LS, Marshall JL, et al. Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. J Clin Oncol 2007;25:4793-9 (Pubitemid 350086483)
48. Leong S, Eckhardt SG, Chan E, et al. A phase I study of sunitinib in combination with modified FOLFOX 6 (mFOLFOX6) chemotherapy [abstract 285]. Presented at: ASCO Gastrointestinal Cancers Symposium; 19-21 January 2007; Orlando, FL
49. ́ Starling N, Vá zquez-MazoF, et al. Phase I study of sunitinib in combination with FOLFIRI in patients with untreated metastatic colorectal cancer. Ann Oncol 2012;23:119-27
50. Mross K, Buchert M, Fasol U, et al. A preliminary report of a Phase II study of folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) plus sunitinib with toxicity, efficacy, pharmacokinetics, biomarker, imaging data in patients with colorectal cancer with liver metastases as 1st line treatment-a study of the CESAR central European Society for Anticancer Drug Research-EWIV**. Int J Clin Pharmacol Ther 2011;1:96-8
51. 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;60:2178-89 (Pubitemid 30225181)
52. Drevs J, Muller-Driver R, Wittig C, et al. PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res 2002;62:4015-22 (Pubitemid 34791068)
53. George D, Jonasch E, Hart L, et al. A phase I, dose escalating and pharmacokinetic (PK) study of the VEGF-receptor inhibitor PTK787/ZK222584 (PTK/ZK) in patients with advanced renal cell or prostate carcinomas. Clin Cancer Res 2001;7:548a
54. Friedman HS, Yung WA, Jackson E, et al. A phase I trial of PTK787/ZK 222584 (PTK/ZK), a novel oral VEGF-R TK inhibitor in patients with recurrent GBM. Clin Cancer Res 2001;7:58a
55. Mross K, Drevs J, Muller M, et al. Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumors. Eur J Cancer 2005;41:1291-9 (Pubitemid 40813005)
56. Thomas AL, Trarbach T, Bartel C, et al. A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK), in combination with FOLFOX4 chemotherapy in patients with advanced colorectal cancer. Ann Oncol 2007;18:782-8 (Pubitemid 46523285)
57. Hecht JR, Trarbach T, Jaeger E, et al. A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic a line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK222584 or placebo (CONFIRM-1). J Clin Oncol 2005;23(Suppl):abstract 3
58. Kohne C, Bajetta E, Lin E, et al. Final results of CONFIRM 2: a multinational, randomized, double-blind, phase III study in 2nd line patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK222584 (PTK/ZK) or placebo. J Clin Oncol 2007;25(Suppl): abstract 4033
59. Fong TA, Shawver LK, Sun L, et al. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 1999;59:99-106 (Pubitemid 29062964)
60. Stopeck A, Sheldon M, Vahedian M, et al. Results of a phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. Clin Cancer Res 2002;8:2798-805 (Pubitemid 35025722)
61. Rosen L, Mulay M, Mayers A, et al. Phase I dose-escalating trial of SU5416, a novel angiogenesis inhibitor, in patients with advanced malignancies. Proc Am Soc Clin Oncol 1999;18:618a
62. Rosen P, Amado R, Hecht J, et al. A phase I/II study of SU5416 in combination with 5-FU/leucovorin in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 2000;18:5a
63. Longo R, Sarmiento R, Fanelli M, et al. Anti-angiogenic therapy: rationale, challenges and clinical studies. Angiogenesis 2002;5:237-56 (Pubitemid 36875123)
64. Cai ZW, Zhang Y, Borzilleri RM, et al. Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f] [1,2,4] triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinase inhibitor (BMS-540215). J Med Chem 2008;51:1976-80 (Pubitemid 351438880)
65. Huynh H, Ngo VC, Fargnoli J, et al. Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clin Cancer Res 2008;14:6146-53
66. Lieu C, Heymach J, Overman M, et al. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res 2011;17:6130-9
67. Ayers M. Comparison of a dual inhibitor of VEGF and FGF signaling, BMS-582664, to the activity of bevacizumab, an inhibitor exclusively of VEGF signaling, in xenograft models of colon carcinoma [abstract]. AACR Meeting Abstr 2007;34:1618
68. Garrett C, Siu L, El-Khoueiry A, et al. A phase I study of brivanib alaninate (BMS-582664), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in combination with full dose cetuximab (BC) in patients (pts) with advanced gastrointestinal malignancies (AGM) who failed prior therapy [abstract]. J Clin Oncol 2008;26(15 Suppl): abstract 4111
69. Ayers M, Awad M, Malone D, et al. Association of K-ras status with efficacy end points from a phase 1/2 study of brivanib in combination with cetuximab in patients with advanced or metastatic colorectal cancer (CRC) [abstract 375]. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers (ASCO-GI) Symposium; 15-17 January 2009; San Francisco, CA
70. Garrett CR, Siu LL, Giaccone G, et al. A phase I study of brivanib alaninate (BMS-582664), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in combination with full dose cetuximab (BC) in patients (pts) with advanced gastrointestinal malignancies (AGM) who failed prior therapy. J Clin Oncol 2008;26(Suppl):abstract #4111
71. Siu LL. Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory K-RAS wildtype (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO.20 trial. 2012 Gastrointestinal Cancers Symposium. J Clin Oncol 2012;30(Suppl 4):abstract 386
72. Kies MS, Blumenschein GR Jr, Christensen O, et al. Phase I study of regorafenib (BAY 73-4506), an inhibitor of oncogenic and angiogenic kinases, administered continuously in patients (pts) with advanced refractory non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol 2010;28(15 Suppl):abstract 7585
73. Strumberg D, Scheulen ME, Frost A, et al. Phase I study of BAY 73-4506, an inhibitor of oncogenic and angiogenic kinases, in patients with advanced refractory colorectal carcinoma (CRC). J Clin Oncol 2009;27(15 Suppl):abstract #3560
74. Grothey A, Sobrero AF, Siena S, et al. Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. J Clin Oncol 2012;30(Suppl 4):abstract LBA385.
75. Wedge SR, Kendrew J, Hennequin LF, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 2005;65:4389-400 (Pubitemid 40775678)
76. Drevs J, Siegert P, Medinger M, et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 2007;25:3045-54 (Pubitemid 47218051)
77. Chen E, Jonker D, Gauthier I, et al. Phase I study of cediranib in combination with oxaliplatin and infusional 5-fluorouracil in patients with advanced colorectal cancer. Clin Cancer Res 2009;15:1481-6
78. Cunningham D, Wong RP, D'haens G, et al. A phase II, double-blind, randomized multicenter study of cediranib with FOLFOX versus bevacizumab with FOLFOX in patients with previously treated metastatic colorectal cancer (mCRC): final PFS results. J Clin Oncol 2008;26(Suppl): abstract #4028
79. Robertson JD, Botwood NA, Rothenberg ML, et al. Phase III trial of FOLFOX plus bevacizumab or cediranib (AZD2171) as first-line treatment of patients with metastatic colorectal cancer: HORIZON III. Clin Colorectal Cancer 2009;8:59-60
80. Hoff PM, Hochhaus A, Pestalozzi B, et al. Cediranib plus FOLFOX/XELOX versus placebo plus FOLFOX/XELOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (Horizon II). ESMO 2010;12:abstract 4035
81. Kerbel RS. Clinical trials of antiangiogenic drugs: opportunities, problems, and assessment of initial results. JCO 2001;19(Suppl 18):45