Anti-VEGF therapies in the clinic

Cold Spring Harbor Perspectives in Medicine

Volumn 2, Issue 10, 2012, Pages

  Meadows, Kellen L ^a   Hurwitz, Herbert I ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AFLIBERCEPT; AXITINIB; BEVACIZUMAB; BRIVANIB ALANINATE; CAPECITABINE; CARBOPLATIN; CEDIRANIB; DEXAMETHASONE; DOCETAXEL; FLUOROURACIL; FOLINIC ACID; GELATINASE B; GEMCITABINE; INTERFERON; IRINOTECAN; LINIFANIB; MITOMYCIN; MOTESANIB; NAVELBINE; PACLITAXEL; PAZOPANIB; PREDNISONE; SEMAXANIB; SORAFENIB; SUNITINIB; TAXANE DERIVATIVE; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN; VATALANIB; ANGIOGENESIS INHIBITOR; TUMOR MARKER; VASCULOTROPIN A;

ANGIOGENESIS; ANTIANGIOGENIC THERAPY; ARTICLE; BREAST CANCER; COLORECTAL CANCER; GASTROINTESTINAL STROMAL TUMOR; GLIOBLASTOMA; HEAD AND NECK CANCER; HUMAN; KIDNEY CANCER; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; NEOPLASM; OVARY CANCER; OVERALL SURVIVAL; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; PROSTATE CANCER; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); SARCOMA; STOMACH CANCER; THYROID CARCINOMA; UPREGULATION; URINARY TRACT CANCER; DRUG ANTAGONISM; DRUG APPROVAL; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; REVIEW; TREATMENT OUTCOME; VASCULARIZATION;

ANGIOGENESIS INHIBITORS; DRUG APPROVAL; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84867591232     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a006577     Document Type: Article

References (141)

1. NCT00393939: A randomized phase 3 study of docetaxel in combination with sunitinib versus docetaxel in the first-line treatment of advanced breast cancer patients. http: //clinicaltrials. gov/ct2/show/NCT00393939.
2. NCT00435409: A randomized, phase 3 study of sunitinib in combination with capecitabine compared with capecitabine in patients with previously treated breast cancer. http: //clinicaltrials. gov/ct2/show/NCT00435409.
3. NCT00449033: A phase III randomized, double-blind, placebo controlled trial comparing the efficacy of gemcitabine, cisplatin and sorafenib to gemcitabine, cisplatin and placebo in first-line treatment of patients with Stage IIIb with effusion and Stage IV non-small cell lung cancer (NSCLC). http: //clinicaltrials. gov/ct2/show/NCT00449033.
4. NCT00700102: A study of avastin (bevacizumab) plus crossover fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer. http: //clinicaltrials. gov/ct2/show/NCT00700102.
5. NCT00777153: Cediranib in combination with lomustine chemotherapy in recurrent glioblastoma (REGAL). http: //clinicaltrials. gov/ct2/show/NCT00777153.
6. NCT00858871: A randomized, double-blind, multi-center phase III study of brivanib versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma. http: //clinicaltrials. gov/ct2/show/NCT00858871.
7. NCT01009593: Efficacy and Tolerability of ABT-869 versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC). http: //clinicaltrials. gov/ct2/show/NCT01009593.
8. Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, AtkinsJN, Seay TE, Fehrenbacher L, Goldberg RM, et al. 2011. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: Results of NSABP protocol C-08. J Clin Oncol 29: 11-16.
9. Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, et al. 2007. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11: 83-95.
10. Beaudry P, Nilsson M, Rioth M, Prox D, Poon D, Xu L, Zweidler-Mckay P, RyanA, Folkman J, Ryeom S, et al. 2008. Potent antitumor effects of ZD6474 on neuroblastoma via dual targeting of tumor cells and tumor endothelium. Mol Cancer Ther 7: 418-424.
11. Bendell JC, Bekaii-Saab TS, Cohn AL, Hurwitz HI, Kozloff M, Tezcan H, Feng S, Flick ED, Sing A, Grothey. 2011. Similarities in treatment (Tx) patterns and clinical outcomes (CO) in patients (pts) with metastatic colorectal cancer (mCRC) initially treated with FOLFOX/BV or FOLFIRI/BV: Results from ARIES, a bevacizumab (BV) observational study. J Clin Oncol 29 (suppl 4; abstr 480). http: //www. asco. org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=10 3&abstractID=70777.
12. Bernaards C, Hegde P, Chen D, Holmgren E, Zheng M, Jubb AM, Koeppen H, Scherer SJ, Chen DS. 2010. Circulating vascular endothelial growth factor (VEGF) as a biomarker for bevacizumab-based therapy in metastatic colorectal, non-small cell lung, and renal cell cancers: Analysis of phase III studies. J Clin Oncol 28: 15s.
13. Bono P, Elfving H, Utriainen T, Osterlund P, Saarto T, Alanko T, Joensuu H. 2009. Hypertension and clinical benefit of bevacizumab in the treatment of advanced renal cell carcinoma. Ann Oncol 20: 393-394.
14. Brufsky A, Bondarenko I, Smirnov V, Hurvitz S, Perez E, Ponomarova O, Vynnychenko I, Swamy R, Mu H, Rivera R. 2009. RIBBON-2: A randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of HER2-negative metastatic breast cancer. Cancer Res69doi: 10. 1158/0008-5472. SABCS-09-42.
15. Burger RA, Brady MF, Bookman MA, Walker JL, Homesley HD, Fowler J, Monk BJ, Greer BE, Boente M, Liang SX. 2010. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol 28: 18.
16. Carmeliet P. 2005. VEGF as a key mediator of angiogenesis in cancer. Oncology 69: 4-10.
17. Cassidy J, Saltz L, Van Cutsem E, Hedrick EE, Lasserre S, Sirzen F, Rohr UP, Hurwitz H. 2010. Venous thromboembolic events with chemotherapy plus bevacizumab: A pooled analysis of over 6, 000 patients in randomized phase II and III studies. J Clin Oncol 28: 15s.
18. Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A. 2003. A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30: 117-124.
19. Crawford Y, Kasman I, Yu L, Zhong C, Wu X, Modrusan Z, Kaminker J, Ferrara N. 2009. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15: 21-34.
20. Cunningham D, Wong RP, D'haens G, Douillard J, Robertson J, Saunders O, Stone AM, Van Cutsem E, HORIZON I Study Group. 2008. 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 26 (20 May suppl; abstr 4028).
21. Dancey J. 2010. mTOR signaling and drug development in cancer. Nat Rev Clin Oncol 7: 209-219.
22. De Boer R, Arrieta Ó, Gottfried M, Blackhall FH, Raats J, Yang CH, Langmuir P, Milenkova T, Read J, Vansteenkiste; J. 2009. Vandetanib plus pemetrexed versus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer (NSCLC): A randomized, double-blind phase III trial (ZEAL). J Clin Oncol 27: 15s.
23. De Gramont A, Van Cutsem E, Tabernero J, Moore MJ, Cunningham D, Rivera F, Im S, Makrutzki M, Shang A, Hoff PM, et al. 2011. AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer. J Clin Oncol 29 (Suppl 4; abstr 362).
24. Docguide. 2010. Addition of sunitinib to FOLFOX6 or FOLFIRI adds no survival benefit for patients with metastatic colorectal cancer. http: //www. docguide. com/addition-sunitinib-folfox6-or-folfiri-adds-no-survival-benefit-patie nts-metastatic-colorectal-cancer.
25. Dowlati A, Gray R, Sandler AB, Schiller JH, Johnson DH. 2008. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab-An Eastern Cooperative Oncology Group Study. Clin Cancer Res 14: 1407-1412.
26. Ebos JM, Lee CR, Christensen JG, Mutsaers AJ, Kerbel RS. 2007. Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc Natl Acad Sci 104: 17069-17074.
27. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. 2009a. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15: 232-239.
28. Ebos JM, Lee CR, Kerbel RS. 2009b. Tumor and host-mediated pathways of resistance and disease progression in response to antiangiogenic therapy. Clin Cancer Res 15: 5020-5025.
29. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, et al. 2007. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356: 125-134.
30. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, et al. 2009. 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 27: 3312-3318.
31. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V. 2010. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): Final analysis of overall survival. J Clin Oncol 28: 2144-2150.
32. Facemire CS, Nixon AB, Griffiths R, Hurwitz H, Coffman TM. 2009. Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide synthase expression. Hypertension 54: 652-658.
33. FDA. 2010. FDA begins process to remove breast cancer indication from Avastin label. http: //www. fda. gov/newsevents/newsroom/pressannouncements/ucm237172. htm.
34. Foernzler D, Delmar P, Kockx M, Cassidy J, Saltz L, Scherer S. 2010. Tumor tissue based biomarker analysis in NO16966: A randomized phase III study of first-line bevacizumab in combination with oxaliplatin-based chemotherapy in patients with mCRC. 2010 Gastrointestinal Cancers Symposium Abstract 374. http: //www. asco. org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=72 &abstractID=2207.
35. Friberg G, Kasza K, Vokes EE, Kindler HL. 2005. Early hypertension (HTN) as a potential pharmacodynamic (PD) marker for survival in pancreatic cancer (PC) patients (pts) treated with bevacizumab (B) and gemcitabine (G). J Clin Oncol 23: 16S.
36. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, et al. 2009. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27: 4733-4740.
37. Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, 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.
38. Gerstner ER, Eichler AF, Plotkin SR, Drappatz J, Doyle CL, Xu L, Duda DG, WenPY, Jain RK, Batchelor TT. 2010. Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide. J Neurooncol 103: 325-332.
39. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB III. 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.
40. Gordon MS, Margolin K, Talpaz M, Sledge GW Jr., Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D. 2001. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19: 843-850.
41. Grothey A, Sugrue MM, Purdie DM, Dong W, Sargent D, Hedrick E, Kozloff M. 2008. 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.
42. Hanahan D, Folkman J. 1996. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353-364.
43. Hanrahan EO, Ryan AJ, Mann H, Kennedy SJ, Langmuir P, Natale RB, Herbst RS, Johnson BE, Heymach JV. 2009. Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. Clin Cancer Res 15: 3600-3609.
44. Hanrahan EO, Lin HY, Kim ES, Yan S, Du DZ, McKee KS, Tran HT, Lee JJ, Ryan AJ, Langmuir P, et al. 2010. Distinct patterns of cytokine and angiogenic factor modulation and markers of benefit for vandetanib and/or chemotherapy in patients with non-small-cell lung cancer. J Clin Oncol 28: 193-201.
45. Hecht JR, Trarbach T, Jaeger E, Hainsworth J, Wolff R, Lloyd K, Bodoky G, BornerM, Laurent D, Jacques C. 2005. A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1). J Clin Oncol 23: 16S.
46. Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, et al. 2009. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27: 672-680.
47. Herbst RS, Heymach JV, O'Reilly MS, Onn A, Ryan AJ. 2007. Vandetanib (ZD6474): An orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert Opin Investig Drugs 16: 239-249.
48. Herbst RS, Sun Y, Eberhardt WE, Germonpre P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, et al. 2010. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): A double-blind, randomised, phase 3 trial. Lancet Oncol 11: 619-626.
49. Holden SN, Eckhardt SG, Basser R, de Boer R, Rischin D, Green M, RosenthalMA, Wheeler C, Barge A, Hurwitz HI. 2005. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol 16: 1391-1397.
50. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, StaroslawskaE, Sosman J, McDermott D, Bodrogi I, et al. 2007. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356: 2271-2281.
51. Hudson CC, Liu M, Chiang GG, Otterness DM, Loomis DC, Kaper F, Giaccia AJ, Abraham RT. 2002. Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol Cell Biol 22: 7004-7014.
52. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, et al. 2004. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335-2342.
53. Hurwitz H, Douglas PS, Middleton JP, Sledge GW, Johnson DH, Reardon DA, Chen D, Rosen O. 2010. Analysis of early hypertension (HTN) and clinical outcome with bevacizumab (BV). J Clin Oncol 28: 15s.
54. Hutson TE, Bukowski RM, Cowey CL, Figlin R, Escudier B, Sternberg CN. 2011. Sequential use of targeted agents in the treatment of renal cell carcinoma. Crit Rev Oncol Hematol 77: 48-62.
55. Jain RK. 2005. Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 307: 58-62.
56. Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT. 2007. Angiogenesis in brain tumours. Nat Rev Neurosci 8: 610-622.
57. Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, Batchelor TT, Sorensen AG. 2009. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 6: 327-338.
58. Johnson K. 2010. Cediranib falls short in phase III glioblastoma trial. Internal Med Newshttp: //www. internalmedicinenews. com/news/neurology/single-article/cediranib-falls-short-in-phase-iii-gli oblastoma-trial/d9b36de685. html.
59. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, JablonsDM, Langer CJ, DeVore RF III., Gaudreault J, Damico LA, et al. 2004. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22: 2184-2191.
60. Jubb AM, Landon TH, Burwick J, Pham TQ, Frantz GD, Cairns B, Quirke P, PealeFV, Hillan KJ. 2003. Quantitative analysis of colorectal tissue microarrays by immunofluorescence and in situ hybridization. J Pathol 200: 577-588.
61. Jubb AM, Hurwitz HI, Bai W, Holmgren EB, Tobin P, Guerrero AS, Kabbinavar F, Holden SN, Novotny WF, Frantz GD, et al. 2006. Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J Clin Oncol 24: 217-227.
62. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, LiebermanG, Griffing S, Bergsland E. 2003. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21: 60-65.
63. Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, Mass R, Perrou B, Nelson B, Novotny WF. 2005. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: Results of a randomized phase II trial. J Clin Oncol 23: 3697-3705.
64. Kang Y, Ohtsu A, Van Cutsem E, Rha SY, Sawaki A, Park S, Lim H, Wu J, LangerB, Shah MA. 2010. AVAGAST: A randomized, double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or placebo in patients with advanced gastric cancer (AGC). J Clin Oncol 28: 18s.
65. Kelly WK, Halabi S, Carducci MA, George DJ, Mahoney JF, Stadler WM, MorrisMJ, Kantoff P, Monk JP III., Small EJ, et al. 2010. A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALGB 90401. J Clin Oncol 28: 18.
66. Kerbel RS. 2008. Tumor angiogenesis. N Engl J Med 358: 2039-2049.
67. Kesmodel SB, Ellis LM, Lin E, Chang GJ, Abdalla EK, Kopetz S, Vauthey JN, Rodriguez-Bigas MA, Curley SA, Feig BW. 2008. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol 26: 5254-5260.
68. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. 1993. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841-844.
69. Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, Innocenti F, Mulcahy MF, O'Reilly E, Wozniak TF, et al. 2010. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: Phase III trial of the cancer and leukemia group B (CALGB 80303). J Clin Oncol doi: 10. 1200/JCO. 2010. 28. 1386.
70. Kohne CH, Cunningham D, Di CF, Glimelius B, Blijham G, Aranda E, ScheithauerW, Rougier P, Palmer M, Wils J, et al. 2002. Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: Results of a multivariate analysis of 3825 patients. Ann Oncol 13: 308-317.
71. Kohne C, Bajetta E, Lin E, Valle JW, Van Cutsem E, Hecht JR, Moore M, GermondCJ, Meinhardt G, Jacques C. 2007. 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/ZK 222584 (PTK/ZK) or placebo. J Clin Oncol 25: 18S.
72. Kolata G. 1998. A cautious awe greets drugs that eradicate tumors in mice. New York Times (3 May 1998).
73. Kopetz S, Hoff PM, Morris JS, Wolff RA, Eng C, Glover KY, Adinin R, OvermanMJ, Valero V, Wen S, 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.
74. +/min mice. Proc Natl Acad Sci 104: 10625-10630.
75. Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, Ashby MA, Dong W, Sugrue MM, Grothey A. 2009. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: The BRiTE observational cohort study. Oncologist 14: 862-870.
76. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, et al. 2009. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27: 740-745.
77. Lieu CH, Tran HT, Jiang Z, Mao M, Overman MJ, Eng C, Morris J, Ellis LM, Heymach J, Kopetz S. 2011. The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer. J Clin Oncol 29(Suppl; abstr 3533).
78. Liu Y, Tran HT, Lin Y, Martin A, Zurita AJ, Sternberg CN, Amado RG, Pandite LN, Heymach J, Team V. 2011. Circulating baseline plasma cytokines and angiogenic factors (CAF) as markers of tumor burden and therapeutic response in a phase III study of pazopanib for metastatic renal cell carcinoma (mRCC). J Clin Oncol 29(Suppl; abstr 4553).
79. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al. 2008. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378-390.
80. Lyman GH, Khorana AA. 2009. Cancer, clots and consensus: New understanding of an old problem. J Clin Oncol 27: 4821-4826.
81. Margolin K, Gordon MS, Holmgren E, Gaudreault J, Novotny W, Fyfe G, AdelmanD, Stalter S, Breed J. 2001. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: Pharmacologic and long-term safety data. J Clin Oncol 19: 851-856.
82. Medical News Today. 2009. http: //www. medicalnewstoday. com/articles/137485. php. Pfizer discontinues global phase III trial of axitinib for futility in advanced pancreatic cancer. http: //www. medicalnewstoday. com/articles/137485. php.
83. Medical News Today. 2010. http: //www. medicalnewstoday. com/articles/208748. php. Pfizer announces positive phase 3 trial results for axitinib in patients with previously-treated metastatic renal cell carcinoma (mRCC). http: //www. medicalnewstoday. com/articles/208748. php.
84. Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P, BukowskiR. 2005. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23: 832-841.
85. Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, et al. 2010a. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28: 3239-3247.
86. Miles DW, de Haas SL, Dirix L, Chan A, Pivot X, Tomczak P, Provencher L, Delmar P, Scherer S. 2010b. Plasma biomarker analyses in the AVADO phase III randomized study of first-line bevacizumab + docetaxel in patients with human epidermal growth factor receptor (her) 2-negative metastatic breast cancer. San Antonio Breast Cancer Symposium December 8-12, 2010.
87. Miles D, Harbeck N, Escudier B, Hurwitz H, Saltz L, Van Cutsem E, Cassidy J, Mueller B, Sirzen F. 2011. Disease course patterns after discontinuation of bevacizumab: Pooled analysis of randomized phase III trials. J Clin Oncol 29: 83-88.
88. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, et al. 2005. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23: 792-799.
89. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, CellaD, Davidson NE. 2007. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357: 2666-2676.
90. Mirshahidi HR, Hsueh CT. 2010. Updates in non-small cell lung cancer-Insights from the 2009 45th annual meeting of the American Society of Clinical Oncology. J Hematol Oncol 3: 18.
91. Monthly Prescribing Reference. 2011. FDA Update on Avastin for metastatic breast cancer. http: //www. empr. com/fda-update-on-avastin-for-metastatic-breast-cancer/article/206504/.
92. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. 2002. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20: 289-296.
93. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, et al. 2007. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356: 115-124.
94. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, et al. 2008. Efficacy of everolimus in advanced renal cell carcinoma: A double-blind, randomised, placebo-controlled phase III trial. Lancet 372: 449-456.
95. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, et al. 2010. Phase 3 trial of everolimus for metastatic renal cell carcinoma: Final results and analysis of prognostic factors. Cancer 116: 4256-4265.
96. Murphy K. 2009. Phase III Sutent trial for colorectal cancer discontinued. Fight Colorectal Cancer Research News. http: //fightcolorectalcancer. org/research_news/2009/07/phase_iii_sutent_trial_for_colorectal_cancer_d iscontinued.
97. Murphy K. 2010. Second Avastin trial shows no benefit in early stage colon cancer. Fight Colorectal Cancer Research News. http: //fightcolorectalcancer. org/research_news/2010/09/second_avastin_trial_shows_no_benefit_in_early_stage_colon_cancer.
98. Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. 2008. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: A meta-analysis. JAMA 300: 2277-2285.
99. Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Langmuir P, Rowbottom JA, Goss GD. 2009. Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: A randomized, double-blind phase III trial (ZEST). J Clin Oncol 27: 15s.
100. Negrier S, Escudier B, Gomez F, Douillard JY, Ravaud A, Chevreau C, Buclon M, Perol D, Lasset C. 2002. Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: A report from the Groupe Francais d'Immunotherapie. Ann Oncol 13: 1460-1468.
101. News Medical. 2010. Pfizer announces discontinuation of SUN 1170 phase 3 study of Sutent in HCC. http: //www. news-medical. net/news/20100423/Pfizer-announces-discontinuation-of-SUN-1170-Phase-3-s tudy-of-Sutent-in-HCC. aspx.
102. Nikolinakos PG, Altorki N, Yankelevitz D, Tran HT, Yan S, Rajagopalan D, Bordogna W, Ottesen LH, Heymach JV. 2010. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res 70: 2171-2179.
103. Nixon A, Allen J, Miller E, Savage S, Kaplan N, Starr M, Bendell J, Uronis H, Fernando N, Hurwitz H. 2007. Clinical evaluation of nitric oxide responses to anti-VEGF therapy with bevacizumab. J Clin Oncol 25: 18S.
104. Nixon A, Starr M, Pang H, Bulusu A, Honeycutt W, Amara A, Bendell JC, HurwitzHI. 2010. Use of plasma angiome to predict PFS in patients with metastatic colorectal cancer (mCRC) treated with capecitabine, oxaliplatin, and bevacizumab (XELOX-A). J Clin Oncol 28 (suppl; abstr e21009).
105. Nixon AB, Pang H, Starr M, Hollis D, Friedman PN, Bertagnolli MM, Kindler HL, Goldberg RM, Venook AP, Hurwitz H. 2011. Prognostic and predictive blood-based biomarkers in patients with advanced pancreatic cancer: Results from CALGB 80303. J Clin Oncol 29 (Suppl; abstr 10508).
106. O'Shaughnessy J, Miles D, Gray RJ, Dieras V, Perez EA, Zon R, Cortes J, Zhou X, Phan S, Miller K. 2010. A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC). J Clin Oncol 28: 15.
107. Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D, Casanovas O. 2009. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15: 220-231.
108. Poon RT, Fan ST, Wong J. 2001. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 19: 1207-1225.
109. Poultsides GA, Servais EL, Saltz LB, Patil S, Kemeny NE, Guillem JG, Weiser M, Temple LK, Wong WD, Paty PB. 2009. Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment. J Clin Oncol 27: 3379-3384.
110. PR News Wire. 2002. http: //www. prnewswire. com/news-releases/pharmacia-announces-closing-of-su5416-semaxanib-clinic al-trials-75895232. html. Pharmacia announces closing of SU5416 (semaxanib) clinical trials. http: //www. prnewswire. com/news-releases/pharmacia-announces-closing-of-su5416-semaxanib-clinic al-trials-75895232. html.
111. PR News Wire. 2010. http: //www. prnewswire. com/news-releases/topline-results-from-phase-3-trial-of-sunitinib-with-e rlotinib-in-advanced-non-small-cell-lung-cancer-nsclc-101330169. html. Topline results from phase 3 trial of sunitinib with erlotinib in advanced non-small cell lung cancer (NSCLC). http: //www. prnewswire. com/news-releases/topline-results-from-phase-3-trial-of-sunitinib-with-e rlotinib-in-advanced-non-small-cell-lung-cancer-nsclc-101330169. html.
112. Ramalingam SS, Belani CP, Mack PC, Vokes EE, Longmate J, Govindan R, Koczywas M, Ivy SP, Gandara DR. 2010. Phase II study of Cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). J Thorac Oncol 5: 1279-1284.
113. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, et al. 2010. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21: 1804-1809.
114. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, Archer L, AtkinsJN, Picus J, Czaykowski P, et al. 2008a. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26: 5422-5428.
115. Rini BI, Schiller JH, Fruehauf JP, Cohen EE, Tarazi JC, Rosbrook B, Ricart AD, Olszanski AJ, Kim S, Spano J. 2008b. Association of diastolic blood pressure (dBP)>90 mmHg with overall survival (OS) in patients treated with axitinib (AG-013736). J Clin Oncol 26 (20 May suppl; abstr 3543).
116. Rixe O, Billemont B, Izzedine H. 2007. Hypertension as a predictive factor of Sunitinib activity. Ann Oncol 18: 1117.
117. Robert NJ, Dieras V, Glaspy J, Brufsky A, Bondarenko I, Lipatov O, Perez E, Yardley D, Zhou X, Phan S. 2009. RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 27: 155.
118. Robertson JD, Botwood NA, Rothenberg ML, Schmoll HJ. 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.
119. Rosenberg JE, Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Bukowski RM, George DJ, Kim ST, Baum CM, Wilding G. 2007. Sunitinib therapy for patients (pts) with metastatic renal cell carcinoma (mRCC): Updated results of two phase II trials and prognostic factor analysis for survival. J Clin Oncol 25: 18S.
120. Ryanne Wu R, Lindenberg PA, Slack R, Noone AM, Marshall JL, He AR. 2009. Evaluation of hypertension as a marker of bevacizumab efficacy. J Gastrointest Cancer 40: 101-108.
121. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, 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.
122. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. 2006. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355: 2542-2550.
123. Sanofi-Aventis. 2009. Phase 3 trial of aflibercept in metastatic pancreatic cancer discontinued. http: //en. sanofi-aventis. com/press/press_releases/2009/ppc_26186. asp.
124. Scagliotti G, Novello S, von Pawel J, Reck M, Pereira JR, Thomas M, Abrao Miziara JE, Balint B, De Marinis F, Keller A, et al. 2010. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol 28: 1835-1842.
125. Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, Kabbinavar F, Novotny W, Sarkar S, Hurwitz H. 2005. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91: 173-180.
126. Scappaticci FA, Skillings JR, Holden SN, Gerber HP, Miller K, Kabbinavar F, Bergsland E, Ngai J, Holmgren E, Wang J, et al. 2007. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99: 1232-1239.
127. Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, Bernasconi S, Saccani S, Nebuloni M, Vago L, et al. 2003. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 198: 1391-1402.
128. Shah MA, Kelsen DP. 2010. Gastric cancer: A primer on the epidemiology and biology of the disease and an overview of the medical management of advanced disease. J Natl Compr Canc Netw 8: 437-447.
129. Shah M, Kang Y-K, Ohtsu A, Delmar P, Foernzler D, Langer B, Scherer S, Van Cutsem E. 2010. Tumour biomarker analyses in the avagast phase III randomized study of first-line bevacizumab + capecitabine/cisplatin in patients with advanced gastric cancer. Ann Oncol 21 (Supplement 8; abstr 174PD).
130. + myeloid cells. Nat Biotechnol 25: 911-920.
131. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W. 2003. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425: 307-311.
132. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, et al. 2010. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28: 1061-1068.
133. Tabernero J, Aranda E, Gomez A, Massuti B, Sastre J, Abad A, Valladares M, Rivera F, Safont M, Diaz-Rubio E. 2010. Phase III study of first-line XELOX plus bevacizumab (BEV) for 6 cycles followed by XELOX plus BEV or single-agent (s/a) BEV as maintenance therapy in patients (pts) with metastatic colorectal cancer (mCRC): The MACRO Trial (Spanish Cooperative Group for the Treatment of Digestive Tumors [TTD]). J Clin Oncol 28: 15s.
134. Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, van Hazel GA, Robinson B, Broad A, Ganju V, Ackland SP, et al. 2010. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 28: 3191-3198.
135. Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, ErdkampFL, Vos AH, van Groeningen CJ, Sinnige HA, et al. 2009. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360: 563-572.
136. Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, Mazier MA, Canon JL, Georgoulias V, Peeters M, et al. 2009a. 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.
137. Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, Verslype C, Scheithauer W, Shang A, Cosaert J, et al. 2009b. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 27: 2231-2237.
138. Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N. 1995. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 95: 1789-1797.
139. Weickhardt AJ, Williams D, Lee C, Simes J, Murone C, Wilson K, Cummins M, Asadi K, Price TJ, Mariadason J, 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; abstr 3531).
140. Yamamoto N, Tamura T, Yamada K, Yamada Y, Nokihara H, Fujiwara Y, Takahashi T, Murakami H, Boku N, Yamazaki K, et al. 2009. Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 64: 1165-1172.
141. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA. 2003. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349: 427-434.