title: 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.
abstract: OBJECTIVE
  To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer.
  
  
  METHODS
  In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m(2)) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks.
  
  
  RESULTS
  Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and 1-year survival was 47%. Bleeding was the most prominent adverse event and was manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and major hemoptysis. Major hemoptysis was associated with squamous cell histology, tumor necrosis and cavitation, and disease location close to major blood vessels.
  
  
  CONCLUSIONS
  Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.
authors.affiliation: Division of Hematology & Oncology, Vanderbilt University Medical School, 777 Preston Research Bldg, Nashville, TN, USA. david.johnson@vanderbilt.edu
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: William F
authors.initials: WF
authors.lastname: Novotny
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
authors.forename: Russell F
authors.initials: RF
authors.lastname: DeVore
authors.forename: Jacques
authors.initials: J
authors.lastname: Gaudreault
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Damico
authors.forename: Eric
authors.initials: E
authors.lastname: Holmgren
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel