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Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?

^a M.D. Anderson Cancer Center, Department of Head and Neck Medical Oncology, Houston, Texas, USA; ^b Vanderbilt University Medical Center, Division of Hematology/Oncology, Nashville, Tennessee, USA

Correspondence: Roy S. Herbst, M.D., M.D. Anderson Cancer Center, Department of Head and Neck Medical Oncology, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. Telephone: 713-792-6363; Fax: 713-796-8655; e-mail: rherbst{at}mdanderson.org

There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC), as progress with current chemotherapy regimens has been limited. The roles of vascular endothelial growth factor (VEGF) in promoting tumor angiogenesis, maintaining existing vasculature, and contributing to resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin^TM; Genentech Inc., South San Fransisco, CA), a monoclonal antibody directed against VEGF, has shown promise in treating a number of different cancers. In a recent phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy produced a significantly longer time to progression (32.1 versus 18.4 weeks) and greater response rate (31% versus 19% [not significant]) than chemotherapy alone. In the subset of patients with nonsquamous histologies, response rates and survival were further enhanced, with a mean survival time of 17.9 months versus 12.3 months with chemotherapy alone.

Bevacizumab was generally well tolerated and did not appear to increase the incidences or severities of the nausea/vomiting, neuropathy, and renal toxicity that are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) appear to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor.

Further work is needed to identify the best way to use bevacizumab in NSCLC, including use in combination with other biologic agents and in the adjuvant setting.

Key Words. Vascular endothelial growth factor • Clinical trial • Non-small cell lung cancer • Monoclonal antibody • Bevacizumab

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