title: A phase II first-line study of gemcitabine, carboplatin, and bevacizumab in advanced stage nonsquamous non-small cell lung cancer.
abstract: BACKGROUND
  Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab.
  
  
  METHODS
  Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity.
  
  
  RESULTS
  From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1-42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8-7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0-16.5). The OS is 57% at 1 year and 10% at 2 years.
  
  
  CONCLUSIONS
  Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate.
authors.affiliation: Division of Oncology, Department of Medicine, Department of Biostatistics, Stanford Cancer Center, Stanford University, Stanford, California 94305-5826, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Clément-Duchêne
authors.forename: Yelena
authors.initials: Y
authors.lastname: Krupitskaya
authors.forename: Kristen
authors.initials: K
authors.lastname: Ganjoo
authors.forename: Philip
authors.initials: P
authors.lastname: Lavori
authors.forename: Alex
authors.initials: A
authors.lastname: McMillan
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.forename: Gary
authors.initials: G
authors.lastname: Zhao
authors.forename: Sukhmani
authors.initials: S
authors.lastname: Padda
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhou
authors.forename: Melanie San
authors.initials: MS
authors.lastname: Pedro-Salcedo
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D016190:Carboplatin; D000093542:Gemcitabine