Papers of particular interest, published recently, have been highlighted as: •• Of major importance

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15. Zhu, Z., P. Bohlen, and L. Witte, Clinical development of angiogenesis inhibitors to vascular endothelial growth factor and its receptors as cancer therapeutics. Curr Cancer Drug Targets, 2002. 2(2): p. 135–56.

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16. •• Gordon, M.S., K. Margolin, M. Talpaz, et al., Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol, 2001. 19(3): p. 843–50.This is a phase 1 study of bevacizumab.

17. Holash, J., S. Davis, N. Papadopoulos, et al., VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A, 2002. 99(17): p. 11393–8.

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18. Byrne, A.T., L. Ross, J. Holash, et al., Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res, 2003. 9(15): p. 5721–8.

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19. Huang, J., J.S. Frischer, A. Serur, et al., Regression of established tumors and metastases by potent vascular endothelial growth factor blockade. Proc Natl Acad Sci U S A, 2003. 100(13): p. 7785–90.

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20. Fukasawa, M. and M. Korc, Vascular endothelial growth factor-trap suppresses tumorigenicity of multiple pancreatic cancer cell lines. Clin Cancer Res, 2004. 10(10): p. 3327–32.

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21. Tew, W.P., M. Gordon, J. Murren, et al., Phase 1 study of aflibercept administered subcutaneously to patients with advanced solid tumors. Clin Cancer Res, 2010. 16(1): p. 358–66.

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22. Lockhart, A.C., M.L. Rothenberg, J. Dupont, et al., Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol. 28(2): p. 207–14.

23. Chu, Q.S., Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors. Expert Opin Biol Ther, 2009. 9(2): p. 263–71.

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24. •• Awada, A., A. Hendlisz, T. Gil, et al., Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer, 2005. 92(10): p. 1855–61.This is a phase 1 study of sorafenib.

25. •• Faivre, S., C. Delbaldo, K. Vera, 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(1): p. 25–35.This is a phase 1 study of sunitinib.

26. •• Britten, C.D., F. Kabbinavar, J.R. Hecht, et al., A phase I and pharmacokinetic study of sunitinib administered daily for 2 weeks, followed by a 1-week off period. Cancer Chemother Pharmacol, 2008. 61(3): p. 515–24.This is a phase 1 study of sunitinib.

27. •• Strumberg, D., H. Richly, R.A. Hilger, et al., Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43–9006 in patients with advanced refractory solid tumors. J Clin Oncol, 2005. 23(5): p. 965–72.This is a phase 1 study of sorafenib.

28. •• Moore, M., H.W. Hirte, L. Siu, et al., Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol, 2005. 16(10): p. 1688–94.This is a phase 1 study of sorafenib.

29. Ton, N.C., G.J. Parker, A. Jackson, et al., Phase I evaluation of CDP791, a PEGylated di-Fab' conjugate that binds vascular endothelial growth factor receptor 2. Clin Cancer Res, 2007. 13(23): p. 7113–8.

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30. Posey, J.A., T.C. Ng, B. Yang, et al., A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma. Clin Cancer Res, 2003. 9(4): p. 1323–32.

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31. Lu, D., X. Jimenez, H. Zhang, et al., Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. Int J Cancer, 2002. 97(3): p. 393–9.

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33. Lu, D., J. Shen, M.D. Vil, et al., Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem, 2003. 278(44): p. 43496–507.

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34. Zhu, Z., K. Hattori, H. Zhang, et al., Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity. Leukemia, 2003. 17(3): p. 604–11.

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35. •• Spratlin, J.L., R.B. Cohen, M. Eadens, 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. 28(5): p. 780–7.This is a phase 1 study of ramucirumab administered weekly.

36. •• Chiorean, E., C. Sweeney, H. Hurwitz, et al., Phase I dose-escalation study of the anti-VEGFR-1 recombinant human IgG1 MAb IMC-1121B administered every other weeks (q2W) or every 3 (q3w) in patients (pts) with advanced cancers. Molecular Targets and Cancer Therapeutics, 2007. Conference Proceedings Abstract B15.This is a phase 1 study of ramucirumab administered every 2 or 3 weeks.

37. •• Garcia, J.A., G.R. Hudes, T.K. Choueiri, et al. Phase II study of IMC-1121B in patients with metastatic renal cancer (mRCC) following VEGFR-2 tyrosine kinase inhibitor (TKI) therapy (IMCL CP12-0605/NCT00515697). in 2010 Genitourinary Cancers Symposium 2010.This is a phase 2 study of ramucirumab in RCC.

38. •• Camidge, D.R., M.S. Ballas, S. Dubey, et al., A phase II, open-label study of ramucirumab (IMC-1121B), an IgG1 fully human monoclonal antibody (MAb) targeting VEGFR-2, in combination with paclitaxel and carboplatin as first-line therapy in patients (pts) with stage IIIb/IV non-small cell lung cancer (NSCLC). J Clin Oncol 2010. 28:15s, 2010 (suppl; abstr 7588).This is a phase 2 study of ramucirumab in lung cancer.

39. •• Carvajal, R.D., M.K. Wong, J.A. Thompson, et al., A phase II randomized study of ramucirumab (IMC-1121B) with or without dacarbazine (DTIC) in patients (pts) with metastatic melanoma (MM). J Clin Oncol 2010. 28:15s, 2010 (suppl; abstr 8519^)This is a phase 2 study of ramucirumab in malignant melanoma.

40. •• Zhu, A.X., R.S. Finn, M. Mulcahy, et al. A phase 2 study of ramucirumab as first-line monotherapy in patients (pts) with advanced hepatocellular carcinoma (HCC): Updated results (CP12-0710/NCT00627042). in International Liver Cancer Association Fourth Annual Conference 2010. Montreal, Quebec, Canada.This is a phase 2 study of ramucirumab in HCC.

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