Antiangiogenesis therapy in the treatment of metastatic colorectal cancer

Therapeutic Advances in Medical Oncology

Volumn 4, Issue 6, 2012, Pages 301-319

  Grothey, Axel ^a   Allegra, Carmen ^b  

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

Aflibercept; antiangiogenesis; bevacizumab; biomarker; clinical trials; metastatic colorectal cancer; regorafenib

Indexed keywords

AFLIBERCEPT; ANGIOGENESIS INHIBITOR; AXITINIB; BEVACIZUMAB; BRIVANIB; CAPECITABINE; CEDIRANIB; CETUXIMAB; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; LINIFANIB; NINTEDANIB; OXALIPLATIN; PANITUMUMAB; PLACEBO; RAMUCIRUMAB; REGORAFENIB; SORAFENIB; SUNITINIB; VANDETANIB; VATALANIB;

ABDOMINAL PAIN; ADVANCED CANCER; AMINOTRANSFERASE BLOOD LEVEL; ANOREXIA; ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; ASTHENIA; BLEEDING; CANCER COMBINATION CHEMOTHERAPY; COLORECTAL CANCER; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DISEASE COURSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; HAND FOOT SYNDROME; HEADACHE; HUMAN; HYPERTENSION; INFECTION; LEUKOPENIA; METASTASIS; MUCOSA INFLAMMATION; NEUROPATHY; NEUTROPENIA; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PREDICTOR VARIABLE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; REVIEW; SIDE EFFECT; STOMATITIS; SURVIVAL RATE; THROMBOEMBOLISM; TREATMENT INDICATION; TREATMENT RESPONSE; ULCER; VOMITING; WOUND HEALING;

EID: 84871879404     PISSN: 17588340     EISSN: 17588359     Source Type: Journal    
DOI: 10.1177/1758834012454464     Document Type: Article

References (95)

1. Adis (2010) Linifanib. Drugs R&D 10: 111–122.
2. Allegra C. Tabernero J. Rougier P. Scagliotti G. Philip P. Lakomy R. (2012) Meta-analysis of anti-VEGF class adverse events from 3 double blind (db) placebo (pbo) controlled phase 3 trials with IV aflibercept (Afl). Presented at 2012 Gastrointestinal Cancers Symposium (ASCO GI), San Francisco, CA, 19–21 January 2012. Abstract 561.
3. Amgen (2007) Amgen discontinues Vectibix(TM) treatment in PACCE trial evaluating Vectibix(TM) as part of triple combination regimen: Preliminary pre-planned interim analysis shows negative effect on progression-free survival [press release]. Amgen, Thousand Oaks, CA, 22 March 2007.
4. Arnold D. Andre T. Bennouna J. Sastre J. Österlund P. Greil R. et al. (2012) Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: Results of a randomized phase III intergroup study (TML study). ASCO Meeting Abstracts 30: CRA3503.
5. Bagri A. Berry L. Gunter B. Singh M. Kasman I. Damico L. et al. (2010) Effects of anti-VEGF treatment duration on tumor growth, tumor regrowth, and treatment efficacy. Clin Cancer Res 16: 3887–3900.
6. Baluk P. Hashizume H. McDonald D. (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15: 102–111.
7. Barleon B. Sozzani S. Zhou D. Weich H. Mantovani A. Marmé D. (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87: 3336–3343.
8. Bates R. Goldsmith J. Bachelder R. Brown C. Shibuya M. Oettgen P. et al. (2003) Flt-1-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids. Curr Biol 13: 1721–1727.
9. Bhargava P. Robinson M. (2011) Development of second-generation VEGFR tyrosine kinase inhibitors: current status. Curr Oncol Rep 13: 103–111.
10. Blackwell K. Hurwitz H. Liebérman G. Novotny W. Snyder S. Dewhirst M. et al. (2004) Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma. Cancer 101: 77–82.
11. Broll R. Erdmann H. Duchrow M. Oevermann E. Schwandner O. Markert U. et al. (2001) Vascular endothelial growth factor (VEGF)–a valuable serum tumour marker in patients with colorectal cancer? Eur J Surg Oncol 27: 37–42.
12. Byrne A. Ross L. Holash J. Nakanishi M. Hu L. Hofmann J. et al. (2003) Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 9: 5721–5728.
13. Carmeliet P. Moons L. Luttun A. Vincenti V. Compernolle V. de Mol M. et al. (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7: 575–583.
14. Chen E. Jonker D. Gauthier I. MacLean M. Wells J. Powers J. et al. (2009) Phase I study of cediranib in combination with oxaliplatin and infusional 5-Fluorouracil in patients with advanced colorectal cancer. Clin Cancer Res 15: 1481–1486.
15. Chiron M. Lejeune P. Bladt F. Vrignaud P. Bissery M. (2008) Broad spectrum of antitumor activity of aflibercept. Presented at American Association for Cancer Research 2008, San Diego, CA, 12–16 April 2008. Abstract 380.
16. Chu Q. (2009) Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors. Expert Opin Biol Ther 9: 263–271.
17. Chun Y. Vauthey J. Boonsirikamchai P. Maru D. Kopetz S. Palavecino M. et al. (2009) Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA 302: 2338–2344.
18. Diaz-Padilla I. Siu L. (2011) Brivanib alaninate for cancer. Expert Opin Investig Drugs 20: 577–586.
19. Díaz-Rubio E. Gómez-España A. Massutí B. Sastre J. Abad A. Valladares M. et al. (2012) First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist 17: 15–25.
20. Dvorak H. Brown L. Detmar M. Dvorak A. (1995) Vascular permeability factor / vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146: 1029–1039.
21. Ebos J. Lee C. Cruz-Munoz W. Bjarnason G. Christensen J. Kerbel R. (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15: 232–239.
22. Escudier B. Eisen T. Stadler W. Szczylik C. Oudard S. Siebels M. et al. (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356: 125–134. Erratum in: (2007) N Engl J Med 357: 203.
23. Fan F. Samuel S. Gaur P. Lu J. Dallas N. Xia L. et al. (2011) Chronic exposure of colorectal cancer cells to bevacizumab promotes compensatory pathways that mediate tumour cell migration. Br J Cancer 104: 1270–1277.
24. Ferrara N. Gerber H. LeCouter J. (2003) The biology of VEGF and its receptors. Nat Med 9: 669–676.
25. Ferrara N. Hillan K. Novotny W. (2005) Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 333: 328–335.
26. Ferrara N. Kerbel R. (2005) Angiogenesis as a therapeutic target. Nature 438: 967–974.
27. Fielding A. Hoff P. Pike L. Wilson D. Robertson J. (2011) Exploration of the effect of treatment to progression with the VEGF signaling inhibitor cediranib (CED) plus chemotherapy (CT) on the results of the HORIZON (HZ) II trial in first-line metastatic colorectal cancer. J Clin Oncol 29(Suppl.): abstract e14052.
28. Fischer C. Mazzone M. Jonckx B. Carmeliet P. (2008) FLT 1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Nat Rev Cancer 8: 942–956.
29. Folkman J. (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29(6 Suppl. 16): 15–18.
30. Formica V. Massara M. Portarena I. Fiaschetti V. Grenga I. Del Vecchio Blanco G. et al. (2009) Role of CA19.9 in predicting bevacizumab efficacy for metastatic colorectal cancer patients. Cancer Biomark 5: 167–175.
31. Fuchs C. Marshall J. Mitchell E. Wierzbicki R. Ganju V. Jeffery M. et al. (2007) Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 25: 4779–4786.
32. Fuchs C. Marshall J. Barrueco J. (2008) Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol 26: 689–690.
33. Garcia V. Garcia J. Silva J. Peña C. Dominguez G. Lorenzo Y. et al. (2008) Levels of VEGF-A mRNA in plasma from patients with colorectal carcinoma as possible surrogate marker of angiogenesis. J Cancer Res Clin Oncol 134: 1165–1171.
34. Garrett C. Siu L. El-Khoueiry A. Buter J. Rocha-Lima C. Marshall J. et al. (2011) Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy. Br J Cancer 105: 44–52.
35. Gerber H. Ferrara N. (2005) Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 65: 671–680.
36. Gerger A. LaBonte M. Lenz H. (2011) Molecular predictors of response to antiangiogenesis therapies. Cancer J 17: 134–141.
37. Giantonio B. Catalano P. Meropol N. O'Dwyer P. Mitchell E. Alberts S. et al. (2007) 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 25: 1539–1544.
38. Goldberg R. Carrato A. (2008) Accomplishments in 2007 in the treatment of advanced colorectal cancer. Gastrointest Cancer Res 2(3 Suppl.): S19–S24.
39. Goldberg R. Rothenberg M. van Cutsem E. Benson A. Blanke C. Diasio R. et al. (2007) The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist 12: 38–50.
40. Grimminger P. Shi M. Barrett C. Lebwohl D. Danenberg K. Brabender J. et al. (2011) TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and -2 clinical trials. Pharmacogenomics J [ePub ahead of print].
41. Grothey A. Galanis E. (2009) Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol 6: 507–518.
42. Grothey A. Hart L. Rowland K. Ansari R. Alberts S. Chowhan N. et al. (2008 a) Intermittent oxaliplatin (oxali) administration and time-to-treatment-failure (TTF) in metastatic colorectal cancer (mCRC): final results of the phase III CONcePT trial. J Clin Oncol 26(Suppl.): abstract 4010.
43. Grothey A. Sobrero A. Siena S. Falcone A. Ychou M. Lenz H. et al. (2012) 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 30(Suppl. 4): abstract LBA385.
44. Grothey A. Sugrue M. Purdie D. Dong W. Sargent D. Hedrick E. et al. (2008 b) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol 26: 5326–5334.
45. Gupta M. (2007) Circulating endothelial cells and circulating endothelial cell progenitors as surrogate markers for determining response to antiangiogenic agents. Clin Colorectal Cancer 6: 337–338.
46. Hecht J. Trarbach T. Hainsworth J. Major P. Jäger E. Wolff R. et al. (2011) 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 29: 1997–2003.
47. Hilberg F. Roth G. Krssak M. Kautschitsch S. Sommergruber W. Tontsch-Grunt U. et al. (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 68: 4774–4782.
48. Hiratsuka S. Maru Y. Okada A. Seiki M. Noda T. Shibuya M. (2001) Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res 61: 1207–1213.
49. Hiratsuka S. Nakamura K. Iwai S. Murakami M. Itoh T. Kijima H. et al. (2002) MMP 9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2 (4): 289–300.
50. Hochster H. Hart L. Ramanathan R. Childs B. Hainsworth J. Cohn A. et al. (2008) Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 26: 3523–3529. Erratum in: (2008) J Clin Oncol 26: 4697.
51. Holash J. Davis S. Papadopoulos N. Croll S. Ho L. Russell M. et al. (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 99: 11393–11398.
52. Huang J. Fischer J. Serur A. Kadenhe A. Yokoi A. McCrudden K. et al. (2003) Regression of established tumors and metastases by potent vascular endothelial growth factor blockade. Proc Natl Acad Sci U S A 100: 7785–7790.
53. Hurwitz H. Fehrenbacher L. Novotny W. Cartwright T. Hainsworth J. Heim W. et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342.
54. Hurwitz H. Yi J. Ince W. Novotny W. Rosen O. (2009) The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncologist 14: 22–28.
55. Jain R. (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307: 58–62.
56. Jayson G. de Haas S. Delmar P. Miles D. Shah M. van Cutsem E. et al (2011) Evaluation of plasma VEGFA as a potential predictive pan-tumour biomarker for bevacizumab. Presented at: 2011 European Multidisciplinary Cancer Congress, Stockholm, Sweden, 23–27 September 2011. Abstract 804.
57. Kopetz S. Hoff P. Morris J. Wolff R. Eng C. Glover K. et al. (2010) Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol 28: 453–459.
58. Koukourakis M. Giatromanolaki A. Sivridis E. Gatter K. Harris A. Tumour Angiogenesis Research Group (2006) Lactate dehydrogenase 5 expression in operable colorectal cancer: strong association with survival and activated vascular endothelial growth factor pathway–a report of the Tumour Angiogenesis Research Group. J Clin Oncol 24: 4301–4308.
59. Lin E. Hassan M. Li Y. Zhao H. Nooka A. Sorenson E. et al. (2007) Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence. Cancer 110: 534–542.
60. Limentani S. Just R. Purdham A. Mulay M. Bair A. Tamby J. et al. (2008) A phase I dose escalation and pharmacokinetic (PK) study of intravenous (iv) aflibercept (VEGF Trap) plus FOLFOX 4 in patients (pts) with advanced solid tumors: preliminary results. Presented at: American Society of Clinical Oncology (ASCO) 2008. Abstract 3556.
61. Lindsay C. MacPherson I. Cassidy J. (2009) Current status of cediranib: the rapid development of a novel anti-angiogenic therapy. Future Oncol 5: 421–432.
62. Lockhart A. Rothenberg M. Dupont J. Cooper W. Chevalier P. Sternas L. et al. (2010) Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol 28: 207–214.
63. Loges S. Mazzone M. Hohensinner P. Carmeliet P. (2009) Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell 15: 167–170.
64. Loupakis F. Cremolini C. Fioravanti A. Orlandi P. Salvatore L. Masi G. et al. (2011) Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer. Br J Cancer 104: 1262–1269.
65. Maglione D. Guerriero V. Viglietto G. Ferraro M. Aprelikova O. Alitalo K. et al. (1993) Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14. Oncogene 8: 925–931.
66. Matsusaka S. Mishima Y. Suenaga M. Terui Y. Kuniyoshi R. Mizunuma N. et al. (2011) Circulating endothelial progenitors and CXCR4-positive circulating endothelial cells are predictive markers for bevacizumab. Cancer 117: 4026–4032.
67. Meyer T. Robles-Carrillo L. Desai H. Hatfield M. Amaya M. Francis J. et al. (2010) Comparison of platelet-activating potential of bevacizumab+VEGF and aflibercept+VEGF complexes. Presented at: ASH 2010, Orlando, FL, 4–7 December 2010. Abstract 3600.
68. Migdal M. Huppertz B. Tessler S. Comforti A. Shibuya M. Reich R. et al. (1998) Neuropilin-1 is a placenta growth factor-2 receptor. J Biol Chem 273: 22272–22278.
69. Olofsson B. Korpelainen E. Pepper M. Mandriota S. Aase K. Kumar V. et al. (1998) Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci U S A 95: 11709–11714.
70. Pàez-Ribes M. Allen E. Hudock J. Takeda T. Okuyama H. Viñals F. et al. (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15: 220–231.
71. Pipp F. Heil M. Issbrücker K. Ziegelhoeffer T. Martin S. van den Heuvel J. et al. (2003) VEGFR-1-selective VEGF homologue PlGF is arteriogenic: evidence for a monocyte-mediated mechanism. Circ Res 92: 378–385.
72. Robertson J. Botwood N. Rothenberg M. Schmoll H. (2009) 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 8: 59–60.
73. Roumen R. Slooter G. Croiset van Uchelen F. Huib L. (2005) Preoperative serum vascular endothelial growth factor is not a marker for subsequent recurrence during long-term follow-up of colorectal cancer patients. Dis Colon Rectum 48: 1070–1075.
74. Saltz L. Clarke S. Díaz-Rubio E. Scheithauer W. Figer A. Wong R. et al. (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26: 2013–2019.
75. Sawano A. Takahashi T. Yamaguchi S. Aonuma M. Shibuya M. (1996) Flt-1 but not KDR/Flk-1 tyrosine kinase is a receptor for placenta growth factor, which is related to vascular endothelial growth factor. Cell Growth Differ 7: 213–221.
76. Schultheis B. Folprecht G. Kuhlmann J. Ehrenberg R. Hacker U. Kohne C. et al. (2011) Phase I study of regorafenib sequentially administered with either FOLFOX or FOLFIRI in patients with first-/second-line colorectal cancer. J Clin Oncol 29(Suppl.): abstract 3585.
77. Siu L. Shapiro J. Jonker D. Karapetis C. Zalcberg J. Simes J. et al. (2012) Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory K-RAS wild-type (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO. 20 trial. J Clin Oncol 30(Suppl. 4): abstract 386.
78. Spratlin J. (2011) Ramucirumab (IMC-1121B): monoclonal antibody inhibition of vascular endothelial growth factor receptor-2. Curr Oncol Rep 13: 97–102.
79. Stathopoulos G. Batziou C. Trafalis D. Koutantos J. Batzios S. Stathopoulos J. et al. (2010) Treatment of colorectal cancer with and without bevacizumab: a phase III study. Oncology 78: 376–381.
80. Tabernero J. van Cutsem E. Lakomy R. Prausova J. Ruff P. van Hazel G. et al. (2011) Results from VELOUR, a phase 3 study of aflibercept versus placebo in combination with FOLFIRI for the treatment of patients with previously treated metastatic colorectal cancer. Presented at: 2011 European Multidisciplinary Cancer Congress, Stockholm, Sweden, 23-27 September 2011. Abstract 6LBA.
81. Tang P. Cohen S. Bjarnason G. Kollmannsberger C. Virik K. MacKenzie M. et al. (2008) 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 26(Suppl.): abstract 4027.
82. Tew W. Gordon M. Murren J. Dupont J. Pezzulli S. Aghajanian C. et al. (2010) Phase 1 study of aflibercept administered subcutaneously to patients with advanced solid tumors. Clin Cancer Res 16: 358–366.
83. Thomas A. Trarbach T. Bartel C. Laurent D. Henry A. Poethig M. et al. (2007) A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor PTK787/ZK222584 (PTK/ZK), in combination with FOLFOX 4 chemotherapy in patients with advanced colorectal cancer. Ann Oncol 18: 782–788.
84. Tol J. Koopman M. Cats A. Rodenburg C. Creemers G. Schrama J. et al. (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. New Engl J Med 360: 563–572.
85. van Cutsem E. Bajetta E. Valle J. Köhne C. Hecht J. Moore M. et al. (2011 a) 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 29: 2004–2010.
86. van Cutsem E. Prenen H. Guillén-Ponce C. Bennouna J. Di Benedetto M. Bouche O. et al. (2011 b) A phase I/II, open-label, randomised study of BIBF 1120 plus mFOLFOX 6 compared to bevacizumab plus mFOLFOX 6 in patients with metastatic colorectal cancer. Presented at: European Multidisciplinary Cancer Congress, Stockholm, Sweden, 23–27 September 2011. Abstract 14LBA.
87. van Cutsem E. Rivera F. Berry S. Kretzschmar A. Michael M. DiBartolomeo M. et al. (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20: 1842–1847.
88. van Cutsem E. Tabernero J. Lakomy R. Prausova J. Ruff P. van Hazel G. et al. (2011 c) Intravenous (IV) 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 22(Suppl. 5): v18; abstract O-0024.
89. Wei S. Liang J. Tsao P. Hsieh F. Yu S. Wong J. (2009) Preoperative serum placenta growth factor level is a prognostic biomarker in colorectal cancer. Dis Colon Rectum 52: 1630–1636.
90. Weickhardt A. Williams D. Lee C. Simes J. Murone C. Wilson K. et al. (2011) Vascular endothelial growth factors (VEGF) and VEGF receptor expression as predictive biomarkers for benefit with bevacizumab in metastatic colorectal cancer (mCRC): Analysis of the phase III MAX study. J Clin Oncol 29(Suppl.): abstract 3531.
91. Wilhelm S. Dumas J. Adnane L. Lynch M. Carter C. Schutz G. et al. (2011) 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 129: 245–255.
92. Willett C. Boucher Y. di Tomaso E. Duda D. Munn L. Tong R. et al. (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10: 145–147. Erratum in: (2004) Nat Med 10: 649.
93. Willett C. Duda D. di Tomaso E. Boucher Y. Ancukiewicz M. Sahani D. et al. (2009) Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 27: 3020–3026.
94. Yin J. Zhang L. Munasinghe J. Linnoila R. Kelly K. (2010) Cediranib/AZD2171 inhibits bone and brain metastasis in a preclinical model of advanced prostate cancer. Cancer Res 70: 8662–8673.
95. Xu L. Duda D. di Tomaso E. Ancukiewicz M. Chung D. Lauwers G. et al. (2009) Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer. Cancer Res 69: 7905–7910.