Emerging antiangiogenic therapies for non-small-cell lung cancer

References

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J. Clin.59(4), 225–249 (2009).
   PubMed Web of Science ®Google Scholar
• American Cancer Society. Cancer Facts & Figures, 2008. American Cancer Society, Inc., Atlanta, GA, USA (2008).
   Google Scholar
• Park JO, Kim SW, Ahn JS et al. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J. Clin. Oncol.25(33), 5233–5239 (2007).
   PubMed Web of Science ®Google Scholar
• Schiller JH, Harrington D, Belani CP et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N. Engl. J. Med.346(2), 92–98 (2002).
   PubMed Web of Science ®Google Scholar
• Smith IE, O’Brien ME, Talbot DC et al. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J. Clin. Oncol.19(5), 1336–1343 (2001).
   PubMed Web of Science ®Google Scholar
• Socinski MA, Schell MJ, Peterman A et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J. Clin. Oncol.20(5), 1335–1343 (2002).
   PubMed Web of Science ®Google Scholar
• von Plessen C, Bergman B, Andresen O et al. Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer. Br. J. Cancer95(8), 966–973 (2006).
   PubMed Web of Science ®Google Scholar
• Scagliotti GV, Parikh P, von Pawel J. et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J. Clin. Oncol.26(21), 3543–3551 (2008).
   PubMed Web of Science ®Google Scholar
• Breathnach OS, Freidlin B, Conley B et al. Twenty-two years of Phase III trials for patients with advanced non-small-cell lung cancer: sobering results. J. Clin. Oncol.19(6), 1734–1742 (2001).
   PubMed Web of Science ®Google Scholar
• Carney DN. Lung cancer – time to move on from chemotherapy. N. Engl. J. Med.346(2), 126–128 (2002).
   PubMed Web of Science ®Google Scholar
• Tarceva® (erlotinib tablets), package insert. Genentech, Inc., CA, USA
   Google Scholar
• Iressa® (gefitinib tablets), package insert. AstraZeneca Pharmaceuticals LP, DE, USA.
   Google Scholar
• Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised Phase III trial. Lancet373(9674), 1525–1531 (2009).
   PubMed Web of Science ®Google Scholar
• Kwak EL, Bang YJ, Camidge DR et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med.363(18), 1693–1703 (2010).
   PubMed Web of Science ®Google Scholar
• Camidge DR, Bang Y, Kwak EL et al. Progression-free survival (PFS) from a Phase I study of crizotinib (PF-02341066) in patients with ALK-positive non-small-cell lung cancer (NSCLC). J. Clin. Oncol.29(Suppl.), (2011) (Abstract 2501).
   Google Scholar
• Riely GJ, Kim D-W, Crino L et al. Phase II data for crizotinib (PF-02341066) in ALK-positive advanced non-small-cell lung cancer (NSCLC): PROFILE 1005. J. Thorac. Oncol.6(Suppl. 2), S411 (2011) (Abstract O31.05).
   PubMed Web of Science ®Google Scholar
• Shaw AT, Yeap B, Solomon B et al. Crizotinib improves overall survival of ALK-positive patients with advanced NSCLC compared with historical controls. J. Thorac. Oncol.6(Suppl. 2), S412 (2011) (Abstract O31.06).
   Google Scholar
• Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat. Med.9(6), 669–676 (2003).
   PubMed Web of Science ®Google Scholar
• Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature407(6801), 249–257 (2000).
   PubMed Web of Science ®Google Scholar
• Folkman J, Klagsbrun M. Vascular physiology. A family of angiogenic peptides. Nature329(6141), 671–672 (1987).
   PubMedGoogle Scholar
• Folkman J, Shing Y. Angiogenesis. J. Biol.Chem.267(16), 10931–10934 (1992).
   PubMed Web of Science ®Google Scholar
• Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell86(3), 353–364 (1996).
   PubMed Web of Science ®Google Scholar
• Kerbel RS. Antiangiogenic therapy: a universal chemosensitization strategy for cancer? Science312(5777), 1171–1175 (2006).
   PubMed Web of Science ®Google Scholar
• Carmeliet P. Angiogenesis in life, disease and medicine. Nature438(7070), 932–936 (2005).
   PubMed Web of Science ®Google Scholar
• Kreuter M, Kropff M, Fischaleck A et al. Prognostic relevance of angiogenesis in stage III NSCLC receiving multimodality treatment. Eur. Respir. J.33(6), 1383–1388 (2009).
   PubMed Web of Science ®Google Scholar
• Meert AP, Paesmans M, Martin B et al. The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br. J. Cancer87(7), 694–701 (2002).
   PubMed Web of Science ®Google Scholar
• Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am. J. Pathol.147(1), 9–19 (1995).
   PubMed Web of Science ®Google Scholar
• Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol.23(5), 1011–1027 (2005).
   PubMed Web of Science ®Google Scholar
• Toi M, Matsumoto T, Bando H. Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. Lancet Oncol.2(11), 667–673 (2001).
   PubMed Web of Science ®Google Scholar
• Kim KJ, Li B, Winer J et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo.Nature362(6423), 841–844 (1993).
   PubMed Web of Science ®Google Scholar
• Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr. Rev.18(1), 4–25 (1997).
   PubMed Web of Science ®Google Scholar
• Fukumura D, Xavier R, Sugiura T et al. Tumor induction of VEGF promoter activity in stromal cells. Cell94(6), 715–725 (1998).
   PubMed Web of Science ®Google Scholar
• Gerber HP, Kowalski J, Sherman D, Eberhard DA, Ferrara N. Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res.60(22), 6253–6258 (2000).
   PubMed Web of Science ®Google Scholar
• Delmotte P, Martin B, Paesmans M et al. [VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis]. Rev. Mal. Respir.19(5 Pt 1), 577–584 (2002).
   PubMed Web of Science ®Google Scholar
• Yuan A, Yu CJ, Kuo SH et al. Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. J. Clin. Oncol.19(2), 432–441 (2001).
   PubMed Web of Science ®Google Scholar
• Millauer B, Longhi MP, Plate KH et al. Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo.Cancer Res.56(7), 1615–1620 (1996).
   PubMed Web of Science ®Google Scholar
• Beitz JG, Kim IS, Calabresi P, Frackelton AR Jr. Human microvascular endothelial cells express receptors for platelet-derived growth factor. Proc. Natl Acad. Sci. USA88(5), 2021–2025 (1991).
   PubMed Web of Science ®Google Scholar
• Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin. Proc.81(9), 1241–1257 (2006).
   PubMed Web of Science ®Google Scholar
• Bergsten E, Uutela M, Li X et al. PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor. Nat. Cell. Biol.3(5), 512–516 (2001).
   PubMed Web of Science ®Google Scholar
• Wu E, Palmer N, Tian Z et al. Comprehensive dissection of PDGF–PDGFR signaling pathways in PDGFR genetically defined cells. PLoSOne.3(11), e3794 (2008).
   Google Scholar
• Levitzki A. PDGF receptor kinase inhibitors for the treatment of PDGF driven diseases. Cytokine Growth Factor Rev.15(4), 229–235 (2004).
   PubMed Web of Science ®Google Scholar
• Pietras K, Rubin K, Sjoblom T et al. Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res.62(19), 5476–5484 (2002).
   PubMed Web of Science ®Google Scholar
• Oikawa T, Onozawa C, Sakaguchi M, Morita I, Murota S. Three isoforms of platelet-derived growth factors all have the capability to induce angiogenesis in vivo.Biol. Pharm. Bull.17(12), 1686–1688 (1994).
   PubMed Web of Science ®Google Scholar
• Risau W, Drexler H, Mironov V et al. Platelet-derived growth factor is angiogenic in vivo.Growth Factors7(4), 261–266 (1992).
   PubMed Web of Science ®Google Scholar
• Hellstrom M, Gerhardt H, Kalen M et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol.153(3), 543–553 (2001).
   PubMed Web of Science ®Google Scholar
• Lindahl P, Johansson BR, Leveen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science277(5323), 242–245 (1997).
   PubMed Web of Science ®Google Scholar
• Abramsson A, Lindblom P, Betsholtz C. Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. J. Clin. Invest.112(8), 1142–1151 (2003).
   PubMed Web of Science ®Google Scholar
• Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C. Role of PDGF-β and PDGFR-β in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development126(14), 3047–3055 (1999).
   PubMed Web of Science ®Google Scholar
• Jain RK, Booth MF. What brings pericytes to tumor vessels? J. Clin. Invest.112(8), 1134–1136 (2003).
   PubMed Web of Science ®Google Scholar
• Dong J, Grunstein J, Tejada M et al. VEGF-null cells require PDGFR α signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J.23(14), 2800–2810 (2004).
   PubMed Web of Science ®Google Scholar
• Brogi E, Wu T, Namiki A, Isner JM. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation90(2), 649–652 (1994).
   PubMedGoogle Scholar
• Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J. Clin. Invest.111(9), 1287–1295 (2003).
   PubMed Web of Science ®Google Scholar
• Erber R, Thurnher A, Katsen AD et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J.18(2), 338–340 (2004).
   PubMed Web of Science ®Google Scholar
• Cabebe E, Wakelee H. Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Curr. Treat. Options Oncol.8(1), 15–27 (2007).
   PubMedGoogle Scholar
• Murakami M, Zheng Y, Hirashima M et al. VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment. Arterioscler. Thromb. Vasc. Biol.28(4), 658–664 (2008).
   PubMed Web of Science ®Google Scholar
• Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R, Rusnati M. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev.16(2), 159–178 (2005).
   PubMed Web of Science ®Google Scholar
• Rusnati M, Presta M. Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti-angiogenesis strategies. Curr. Pharm. Des.13(20), 2025–2044 (2007).
   PubMed Web of Science ®Google Scholar
• Gerritsen ME, Soriano R, Yang S et al. Branching out: a molecular fingerprint of endothelial differentiation into tube-like structures generated by Affymetrix oligonucleotide arrays. Microcirculation10(1), 63–81 (2003).
   PubMedGoogle Scholar
• Klein S, Giancotti FG, Presta M, Albelda SM, Buck CA, Rifkin DB. Basic fibroblast growth factor modulates integrin expression in microvascular endothelial cells. Mol. Biol. Cell4(10), 973–982 (1993).
   PubMed Web of Science ®Google Scholar
• Underwood PA, Bean PA, Gamble JR. Rate of endothelial expansion is controlled by cell:cell adhesion. Int. J. Biochem. Cell Biol.34(1), 55–69 (2002).
   PubMedGoogle Scholar
• Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell8(4), 299–309 (2005).
   PubMed Web of Science ®Google Scholar
• Kano MR, Morishita Y, Iwata C et al. VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRβ signaling. J. Cell Sci.118(Pt 16), 3759–3768 (2005).
   PubMed Web of Science ®Google Scholar
• Nissen LJ, Cao R, Hedlund EM et al. Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. J. Clin. Invest.117(10), 2766–2777 (2007).
   PubMed Web of Science ®Google Scholar
• Johnson DH, Fehrenbacher L, Novotny WF et al. 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(11), 2184–2191 (2004).
   PubMed Web of Science ®Google Scholar
• Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med.355(24), 2542–2550 (2006).
   PubMed Web of Science ®Google Scholar
• Ramalingam SS, Dahlberg SE, Langer CJ et al. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J. Clin. Oncol.26(1), 60–65 (2008).
   PubMed Web of Science ®Google Scholar
• Reck M, von Pawel J, Zatloukal P et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAiL. J. Clin. Oncol.27(8), 1227–1234 (2009).
   PubMed Web of Science ®Google Scholar
• Reck M, von Pawel J, Zatloukal P et al. 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(9), 1804–1809 (2010).
   PubMed Web of Science ®Google Scholar
• Leighl NB, Zatloukal P, Mezger J et al. Efficacy and safety of bevacizumab-based therapy in elderly patients with advanced or recurrent nonsquamous non-small-cell lung cancer in the Phase III BO17704 study (AVAiL). J. Thorac. Oncol.5(12), 1970–1976 (2010).
   PubMed Web of Science ®Google Scholar
• Thomas M, Reuss A, Fischer JR et al. Innovations: Randomized Phase II trial of erlotinib (E)/bevacizumab (B) compared with cisplatin (P)/gemcitabine (G) plus B in first-line treatment of advanced nonsquamous (NS) non-small-cell lung cancer (NSCLC). J. Clin. Oncol.29(15S), (2011) (Abstract 7504).
   Google Scholar
• Miller VA, O’Conner P, Soh C, Kabbinavar F; for the ATLAS Investigators. A randomized, double-blind, placebo-controlled, Phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for first-line treatment of locally advanced, recurrent, or metastatic non-small-cell lung cancer (NSCLC). J. Clin. Oncol.27(18S), (2009) (Abstract LBA8002).
   Google Scholar
• Kabbinavar FF, Miller VA, Johnson BE, O’Connor PG, Soh C; ATLAS. Overall survival (OS) in ATLAS, a Phase IIIb trial comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy (chemo) with B for first-line treatment of locally advanced, recurrent, or metastatic non-small-cell lung cancer (NSCLC). J. Clin. Oncol.28(15s), (2010) (Abstract 7526).
   Google Scholar
• Ardizzoni A, Boni L, Tiseo M et al. Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J. Natl Cancer Inst.99(11), 847–857 (2007).
   PubMed Web of Science ®Google Scholar
• Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M. Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer. J. Clin. Oncol.22(19), 3852–3859 (2004).
   PubMed Web of Science ®Google Scholar
• Patel JD, Hensing TA, Rademaker A et al. Phase II study of pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer. J. Clin. Oncol.27(20), 3284–3289 (2009).
   PubMed Web of Science ®Google Scholar
• Patel JD, Bonomi P, Socinski MA et al. Treatment rationale and study design for the pointbreak study: a randomized, open-label Phase III study of pemetrexed/carboplatin/bevacizumab followed by maintenance pemetrexed/bevacizumab versus paclitaxel/carboplatin/bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. Clin. Lung Cancer10(4), 252–256 (2009).
   PubMed Web of Science ®Google Scholar
• Crino L, Dansin E, Garrido P et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a Phase 4 study. Lancet Oncol.11(8), 733–740 (2010).
   PubMed Web of Science ®Google Scholar
• Wozniak AJ, Garst J, Jahanzeb M et al. Clinical outcomes (CO) for special populations of patients (pts) with advanced non-small-cell lung cancer (NSCLC): results from ARIES, a bevacizumab (BV) observational cohort study (OCS). J. Clin. Oncol.28(7s), (2010) (Abstract 7618).
   Google Scholar
• 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.28(2), 207–214 (2010).
   PubMed Web of Science ®Google Scholar
• Novello S, Ramlau R, Gorbunova VA et al. Aflibercept in combination with docetaxel for second-line treatment of locally advanced or metastatic non-small-cell lung cancer (NSCLC): final results of a multinational placebo-controlled Phase III trial (EFC10261-VITAL). Abstract associated with oral presentation at: The 14th Biennial World Conference on Lung Cancer. Amsterdam, The Netherlands, 3–7 July 2011 (Abstract O43.06).
   Google Scholar
• 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.28(5), 780–787 (2010).
   PubMed Web of Science ®Google Scholar
• Camidge DR, Ballas MS, Dubey S 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.28(15S), (2010) (Abstract 7588).
   PubMedGoogle Scholar
• Wilhelm SM, Carter C, Tang L et al. BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res.64(19), 7099–7109 (2004).
   PubMed Web of Science ®Google Scholar
• Blumenschein GR Jr, Gatzemeier U, Fossella F et al. Phase II, multicenter, uncontrolled trial of single-agent sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer. J. Clin. Oncol.27(26), 4274–4280 (2009).
   PubMed Web of Science ®Google Scholar
• Scagliotti G, Novello S, von Pawel J et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J. Clin. Oncol.28(11), 1835–1842 (2010).
   PubMed Web of Science ®Google Scholar
• Gatzemeier U, Eisen T, Santoro A et al. Sorafenib (S) gemcitabine/cisplatin (GC) vs GC alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC): Phase III NSCLC research experience utilizing sorafenib (NEXUS) trial [abstract]. Ann. Oncol.21(Suppl. 8), viii7 (2010).
   Google Scholar
• Schiller JH, Lee JW, Hanna NH, Traynor AM, Carbone DP. A randomized discontinuation Phase II study of sorafenib versus placebo in patients with non-small-cell lung cancer who have failed at least two prior chemotherapy regimens: E2501. J. Clin. Oncol.26(15S), (2008) (Abstract 8014).
   Google Scholar
• Socinski MA, Novello S, Brahmer JR et al. Multicenter, Phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J. Clin. Oncol.26(4), 650–656 (2008).
   PubMed Web of Science ®Google Scholar
• Novello S, Scagliotti GV, Rosell R et al. Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small-cell lung cancer. Br. J. Cancer101(9), 1543–1548 (2009).
   PubMed Web of Science ®Google Scholar
• Hilberg F, Roth GJ, Krssak M et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res.68(12), 4774–4782 (2008).
   PubMed Web of Science ®Google Scholar
• Roth GJ, Heckel A, Colbatzky F et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J. Med. Chem.52(14), 4466–4480 (2009).
   PubMed Web of Science ®Google Scholar
• Reck M, Kaiser R, Eschbach C et al. A Phase II double-blind study to investigate efficacy and safety of two doses of the triple angiokinase inhibitor BIBF 1120 in patients with relapsed advanced non-small-cell lung cancer. Ann. Oncol.22(6), 1374–1381 (2011).
   PubMed Web of Science ®Google Scholar
• Wedge SR, Ogilvie DJ, Dukes M et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res.62(16), 4645–4655 (2002).
   PubMed Web of Science ®Google Scholar
• Natale RB, Bodkin D, Govindan R et al. Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized Phase II study. J. Clin. Oncol.27(15), 2523–2529 (2009).
   PubMed Web of Science ®Google Scholar
• De Boer RH, Arrieta O, Yang CH et al. Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind Phase III trial. J. Clin. Oncol.29(8), 1067–1074 (2011).
   PubMed Web of Science ®Google Scholar
• Herbst RS, Sun Y, Eberhardt WE et al. 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(7), 619–626 (2010).
   PubMed Web of Science ®Google Scholar
• Natale RB, Thongprasert S, Greco FA et al. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J. Clin. Oncol.29(8), 1059–1066 (2011).
   PubMed Web of Science ®Google Scholar
• Lee J, Hirsh V, Park K et al. Vandetanib versus placebo in patients with advanced non-small-cell lung cancer (NSCLC) after prior therapy with an EGFR tyrosine kinase inhibitor (TKI): a randomized, double-blind Phase III trial (ZEPHYR). J. Clin. Oncol.28(15s), (2010) (Abstract 7525).
   Google Scholar
• Nikolinakos P, Heymach JV. The tyrosine kinase inhibitor cediranib for non-small-cell lung cancer and other thoracic malignancies. J. Thorac. Oncol.3(6 Suppl. 2), S131–S134 (2008).
   PubMed Web of Science ®Google Scholar
• Goss GD, Arnold A, Shepherd FA et al. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC Clinical Trials Group BR24 study. J. Clin. Oncol.28(1), 49–55 (2010).
   PubMed Web of Science ®Google Scholar
• Gadgeel SM, Ruckdeschel JC, Wozniak AJ et al. Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small-cell lung cancer (NSCLC). J. Clin. Oncol.29(Suppl.), (2011) (Abstract 7564).
   PubMedGoogle Scholar
• Polverino A, Coxon A, Starnes C et al. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res.66(17), 8715–8721 (2006).
   PubMed Web of Science ®Google Scholar
• Blumenschein GR Jr, Kabbinavar F, Menon H et al. A Phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Ann. Oncol.22(9), 2057–2067 (2011).
   PubMed Web of Science ®Google Scholar
• Scagliotti G, Vynnychenko I, Ichinose Y et al. An international, randomized, placebo-controlled, double-blind Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). J. Clin. Oncol.29(Suppl.), (2011) (Abstract LBA7512).
   Google Scholar
• Kumar R, Knick VB, Rudolph SK et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol. Cancer Ther.6(7), 2012–2021 (2007).
   PubMed Web of Science ®Google Scholar
• Podar K, Tonon G, Sattler M et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proc. Natl. Acad. Sci. USA103(51), 19478–19483 (2006).
   PubMed Web of Science ®Google Scholar
• Choueiri TK. Axitinib, a novel antiangiogenic drug with promising activity in various solid tumors. Curr. Opin. Investig. Drugs9(6), 658–671 (2008).
   PubMed Web of Science ®Google Scholar
• Schiller JH, Larson T, Ou SH et al. Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a Phase II study. J. Clin. Oncol.27(23), 3836–3841 (2009).
   PubMed Web of Science ®Google Scholar
• Gridelli C, Rossi A, Maione P et al. Vascular disrupting agents: a novel mechanism of action in the battle against non-small-cell lung cancer. Oncologist14(6), 612–620 (2009).
   PubMed Web of Science ®Google Scholar
• McKeage MJ, Reck M, Jameson MB et al. Phase II study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) combined with carboplatin and paclitaxel in previously untreated advanced non-small-cell lung cancer. Lung Cancer65(2), 192–197 (2009).
   PubMed Web of Science ®Google Scholar
• McKeage MJ, von Pawel J, Reck M et al. Randomised Phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small-cell lung cancer. Br. J. Cancer99(12), 2006–2012 (2008).
   PubMed Web of Science ®Google Scholar
• Lara PN Jr, Douillard JY, Nakagawa K et al. Randomized Phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J. Clin. Oncol.29(22), 2965–2971 (2011).
   PubMed Web of Science ®Google Scholar
• Mauer AM, Cohen EE, Ma PC et al. A Phase II study of ABT-751 in patients with advanced non-small-cell lung cancer. J. Thorac. Oncol.3(6), 631–636 (2008).
   PubMed Web of Science ®Google Scholar
• Rudin CM, Mauer A, Smakal M et al. Phase I/II study of pemetrexed with or without ABT-751 in advanced or metastatic non-small-cell lung cancer. J. Clin. Oncol.29(8), 1075–1082 (2011).
   PubMed Web of Science ®Google Scholar
• Garmy-Susini B, Varner JA. Roles of integrins in tumor angiogenesis and lymphangiogenesis. Lymphat. Res. Biol.6(3–4), 155–163 (2008).
   PubMedGoogle Scholar
• Silva R, D’Amico G, Hodivala-Dilke KM, Reynolds LE. Integrins: the keys to unlocking angiogenesis. Arterioscler.Thromb. Vasc. Biol.28(10), 1703–1713 (2008).
   PubMed Web of Science ®Google Scholar
• Brooks PC, Montgomery AM, Rosenfeld M et al. Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell79(7), 1157–1164 (1994).
   PubMed Web of Science ®Google Scholar
• Kumar CC, Malkowski M, Yin Z et al. Inhibition of angiogenesis and tumor growth by SCH221153, a dual α(v)β3 and α(v)β5 integrin receptor antagonist. Cancer Res.61(5), 2232–2238 (2001).
   PubMed Web of Science ®Google Scholar
• Gogali A, Charalabopoulos K, Constantopoulos S. Integrin receptors in primary lung cancer. Exp. Oncol.26(2), 106–110 (2004).
   PubMed Web of Science ®Google Scholar
• Delbaldo C, Raymond E, Vera K et al. Phase I and pharmacokinetic study of etaracizumab (Abegrin), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors. Invest. New Drugs26(1), 35–43 (2008).
   PubMed Web of Science ®Google Scholar