title: Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer.
abstract: BACKGROUND
  The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer.
  
  
  METHODS
  Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m(2) and carboplatin at an area under the concentration-time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression.
  
  
  RESULTS
  In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment-related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow-up of 15.8 months, the median progression-free survival was 7.1 months (95% confidence interval, 5.9-8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8-25.5 months).
  
  
  CONCLUSIONS
  Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer.
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA. james.stevenson@uphs.upenn.edu
authors.forename: James P
authors.initials: JP
authors.lastname: Stevenson
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Somer
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Evans
authors.forename: Kumar
authors.initials: K
authors.lastname: Rajagopalan
authors.forename: Kimberly
authors.initials: K
authors.lastname: Krieger
authors.forename: Mona
authors.initials: M
authors.lastname: Jacobs-Small
authors.forename: Nikolas
authors.initials: N
authors.lastname: Dyanick
authors.forename: Barry
authors.initials: B
authors.lastname: Milcarek
authors.forename: Susan
authors.initials: S
authors.lastname: Coakley
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
authors.forename: Beth
authors.initials: B
authors.lastname: Eaby-Sandy
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hageboutros
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D060046:Maintenance Chemotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin