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Review: The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer

Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery F. Magrassi and A. Lanzara, Second University of Naples, Italy, Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy

Maria Anna Bareschino

Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery F. Magrassi and A. Lanzara, Second University of Naples, Italy, Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy

Antonio Rossi

Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy

Paolo Maione

Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy

Vincenzo Castaldo

Direzione Sanitaria, S.G. Moscati Hospital, Avellino, Italy

Nicole Mazzeo

Pharmacy Unit S.G. Moscati Hospital, Avellino, Italy

Paola Claudia Sacco

Sacco Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy

Marianna Luciana Ferrara

Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery F. Magrassi and A. Lanzara, Second University of Naples, Italy

Giovanni Palazzolo

Operative Unit Medical Oncology U.L.S.S. 15 Cittadella, Padova, Italy

Fortunato Ciardiello

Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery F. Magrassi and A. Lanzara, Second University of Naples, Italy

Cesare Gridelli

Division of Medical Oncology, S.G. Moscati Hospital, Città Ospedaliera, Contrada Amoretta, 83100 Avellino, Italy, cgridelli{at}libero.it

Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection - in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease.

Key Words: non-small cell lung cancer • angiogenesis • vascular endothelial growth factor • bevacizumab

References

• Arriagada, R., Bergman, B., Dunant, A., Le Chevalier, T., Pignon, J.P., Vansteenkiste, J. and International Adjuvant Lung Cancer Trial Collaborative Group (2004) Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 350: 351-360.[Abstract/Free Full Text]
• Douillard, Y., Rosell, R., De Lena, M., Carpagnano, F., Ramlau, R., Gonzáles-Larriba, J.L. et al. (2006) Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 7: 719-727.[CrossRef][Medline] [Order article via Infotrieve]
• Ferrara, N. (1999) Molecular and biological properties of vascular endothelial growth factor. J Mol Med 77: 527-543.[CrossRef][Medline] [Order article via Infotrieve]
• Ferrara, N., Gerber, H.P. and LeCouter, J. (2003) The biology of VEGF and its receptors. Nat Med 9: 669-676.[CrossRef][Medline] [Order article via Infotrieve]
• Gatzemeier, U., Pluzanska, A., Szczesna, A., Kaukel, E., Roubec, J., De Rosa, F. et al. (2007) Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: The Tarceva Lung Cancer Investigation Trial. J Clin Oncol 25: 1545-1552.[Abstract/Free Full Text]
• Giaccone, G., Herbst, R.S., Manegold, C., Scagliotti, G., Rosell, R., Miller, V. et al. (2004) Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT 1. J Clin Oncol 22: 777-784.[Abstract/Free Full Text]
• Govindan, R., Bogart, J. and Vokes, E.E. (2008) Locally advanced non-small cell lung cancer: the past, present, and future. J Thorac Oncol 3: 917-928.[Medline] [Order article via Infotrieve]
• Herbst, R.S., Giaccone, G., Schiller, J.H., Natale, R.B., Miller, V., Manegold, C. et al. (2004) Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT 2. J Clin Oncol 22: 785-794.[Abstract/Free Full Text]
• Herbst, R.S., Onn, A. and Sandler, A. (2005) Angiogenesis and lung cancer: Prognostic and therapeutic implications. J Clin Oncol 23: 3243-3256.[Abstract/Free Full Text]
• Herbst, R.S., Prager, D., Hermann, R., Fehrenbacher, L., Johnson, B.E., Sandler, A. et al. (2005) TRIBUTE: A phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel
• chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 23: 5892-5899.
• Hicklin, D.J. and Ellis, L.M. (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23: 1011-1027.[Abstract/Free Full Text]
• Houck, K., Ferrara, N., Winer, J., Cachianes, G., Li, B. and Leung, D.W. (1991) The vascular endothelial growth factor family: Identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5: 1806-1814.[Abstract/Free Full Text]
• Jain, R.K. (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307: 58-62.[Abstract/Free Full Text]
• Johnson, D.H., Fehrenbacher, L., Novotny, W.F., Herbst, R.S., Nemunaitis, J.J., Jablons, D.M. 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.[Abstract/Free Full Text]
• Keller, S.M., Adak, S., Wagner, H., Herskovic, A., Komaki, R., Brooks, B.J. et al. (2000) Eastern Cooperative Oncology Group. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med 343: 1217-1222.[Abstract/Free Full Text]
• Maione, P., Gridelli, C., Troiani, T. and Ciardiello, F. (2006) Combining target therapies and drugs with multiple target in the treatment of NSCLC. The Oncologist 11: 274-284.[Abstract/Free Full Text]
• Manegold, C., Von Pawel, J., Zatloukal, P., Ramlau, R., Gorbounova, V., Hirsh, V. et al. (2008) BO17704 (AVAIL): a phase III randomised study of first-line bevacizumab combined with cisplatin/gemcitabine (CG) in patients (pts) with advanced or recurrent non-squamous, non-small cell lung cancer (NSCLC). Annal of Oncol 19: LAB1 abstr.
• Meert, A.P., Paesmans, M., Martin, B., Delmotte, P., Berghmans, T., Verdebout, J.M. et al. (2002) The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 87: 694-701.[CrossRef][Medline] [Order article via Infotrieve]
• Morgensztern, D. and Govindan, R. (2006) Clinical trials of antiangiogenic therapy in non-small cell lung cancer: focus on bevacizumab and ZD6474. Expert Rev Anticancer Ther 6: 545-551.[CrossRef][Medline] [Order article via Infotrieve]
• Paavonen, K., Puolakkainen, P., Jussila, L., Jahkola, T. and Alitalo, K. (2000) Vascular endothelial growth factor receptor-3 in lymphangiogenesis in wound healing. Am J Pathol 156: 1499-1504.[Abstract/Free Full Text]
• Parkin, D.M., Bray, F., Ferlay, J. and Pisani, P. (2000) Estimating the world cancer burden: Globocan. Int J Cancer 94: 153-156.[CrossRef]
• Pignon, J.P., Tribodet, H., Scagliotti, G.V., Douillard, J.Y., Shepherd, F.A., Stephens, R.J. et al. (2006) Lung Adjuvant Cisplatin Evaluation (LACE): A pooled analysis of five randomized clinical trials including 4,584 patients. J Clin Oncol 24: 7008 abstr.
• Ponn, R.B., Lo Cicero, J. Iii and Daly, B.D.T. (2005) Surgical treatment of non small cell lung cancer. In: Shields, T.W., Lo Cicero, J.Iii, Ponn, R., Rusch, V.W. (eds), General thoracic surgery, 6th edn. Philadelphia: Lippincot Williams and Wilkin, pp. 1548-1587.
• Reck, M., von Pawel, J., Zatloukal, P., Ramlau, R., Gorbounova, V., Hirsh, V. et al. (2009) 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: 1227-1234.[Abstract/Free Full Text]
• Rizvi, N.A., Rusch, V., Zhao, B., Senturk, E., Schwartz, L., Fury, M. et al. (2007) Single agent bevacizumab and bevacizumab in combination with docetaxel and cisplatin as induction therapy for resectable IB-IIIA non-small cell lung cancer. J Clin Oncol 25: 18045 abstr.
• Sandler, A., Gray, R., Perry, M.C., Brahmer, J., Schiller, J.H., Dowlati, A. et al. (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355: 2542-2550.[Abstract/Free Full Text]
• Scagliotti, G.V., Fossati, R., Torri, V., Crinò, L., Giaccone, G., Silvano, G. et al. (2003) Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer. J Natl Cancer Inst 95: 1453-1461.[Abstract/Free Full Text]
• Socinski, M.A., Morris, D.E., Stinchcombe, T.E., Halle, J.S., Moore, D.T., Tynan, M.T. et al. (2008) Incorporation of bevacizumab (B) and erlotinib (Er) with induction (I) and concurrent (C) carboplatin (Cb)/paclitaxel (P) and 74 Gy of thoracic radiotherapy in stage III non-small cell lung cancer (NSCLC). J Clin Oncol 26: 7517 abstr.
• Strauss, G.M., Herndon, J.E., Maddaus, M.A., Johnstone, D.W., Johnson, E.A., Watson, D.M. et al. (2006) Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update on Cancer and Leukemia Group B (CALGB) protocol 9633. J Clin Oncol 24: 7007 abst.
• Waller, D., Peake, M.D., Stephens, R.J., Gower, N.H., Milroy, R., Parmar, M.K. et al. (2004) Chemotherapy for patients with non-small cell lung cancer: The surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg 26: 173-182.[Abstract/Free Full Text]
• Winton, T., Livingston, R., Johnson, D., Rigas, J., Johnston, M., Butts, C. et al. (2005) Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 352: 2589-2597.[Abstract/Free Full Text]

Therapeutic Advances in Medical Oncology, Vol. 1, No. 1, 5-13 (2009)
DOI: 10.1177/1758834009338635


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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Schettino, C. Articles by Gridelli, C. Social Bookmarking                         What's this?