title: Phase II Trial of Dose-dense Pemetrexed, Gemcitabine, and Bevacizumab in Patients With Advanced, Non-Small-cell Lung Cancer.
abstract: Platinum-based chemotherapy is standard for untreated, advanced non-small-cell lung cancer (NSCLC). We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine, and bevacizumab in patients with advanced NSCLC.
  
  
  
  This multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (400 mg/m2), gemcitabine (1200 mg/m2), and bevacizumab (10 mg/kg), given every 14 days in patients with untreated, advanced NSCLC. The primary endpoint was progression-free survival with secondary endpoints of response rate and overall survival.
  
  
  
  Thirty-nine patients were enrolled. Treatment was well tolerated; the most common grade 3-4 toxicities were neutropenia and fatigue. Of the 38 patients evaluable for tumor response, 1 (3%) had complete response, 15 (39%) had partial response, 12 (31%) had stable disease, and 10 (26%) had progressive disease. Median progression-free survival was 6.1 months (95% confidence interval [CI], 4.2-7.9) and median overall survival was 18.4 months (95% CI, 13.1-29.5). The 1-year overall survival rate was 64% (95% CI, 51%-81%) and the 2-year overall survival rate was 41% (95% CI, 28%-60%).
  
  
  
  Treatment with dose-dense pemetrexed, gemcitabine, and bevacizumab met the primary endpoint with promising efficacy and a manageable safety profile in patients with untreated advanced NSCLC. This regimen represents a reasonable therapeutic option.
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI. Electronic address: bryansch@med.umich.edu.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Schneider
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Kalemkerian
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Shirish M
authors.initials: SM
authors.lastname: Gadgeel
authors.affiliation: Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI.
authors.forename: Manuel
authors.initials: M
authors.lastname: Valdivieso
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Hackstock
authors.affiliation: Biostatistics Core, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Biostatistics Core, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Lance K
authors.initials: LK
authors.lastname: Heilbrun
authors.affiliation: Synergy Cancer Center, Las Vegas, NV.
authors.forename: John C
authors.initials: JC
authors.lastname: Ruckdeschel
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Antoinette J
authors.initials: AJ
authors.lastname: Wozniak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054796:Drug Dosage Calculations; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000178:diet therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000068437:Pemetrexed; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine
keywords: Adenocarcinoma of the lung; Dose-dense chemotherapy; Frontline chemotherapy; Nonplatinum; VEGF inhibition