title: Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study.
abstract: OBJECTIVE
  The efficacy of cisplatin, irinotecan, and bevacizumab was evaluated in patients with extensive-stage small-cell lung cancer (ES-SCLC).
  
  
  METHODS
  Patients with ES-SCLC received cisplatin 30 mg/m(2) and irinotecan 65 mg/m(2) on days 1 and 8 plus bevacizumab 15 mg/kg on day 1 every 21 days for six cycles on this phase II study. The primary end point was to differentiate between 50% and 65% 12-month survival rates.
  
  
  RESULTS
  Seventy-two patients were enrolled between March 2005 and April 2006; four patients canceled, and four were ineligible. Grade 3 or 4 toxicities included neutropenia (25%), all electrolyte (23%), diarrhea (16%), thrombocytopenia (10%), fatigue (10%), nausea (10%), hypertension (9%), anemia (9%), infection (7%), vascular access thrombosis (2%), stroke (2%), and bowel perforation (1%). Three deaths (5%) occurred on therapy as a result of pneumonitis (n = 1), stroke (n =1), and heart failure (n = 1). Complete response, partial response, and stable disease occurred in three (5%), 45 (70%), and 11 patients (17%), respectively. Progressive disease occurred in one patient (2%). Overall response rate was 75%. Median progression-free survival (PFS) was 7.0 months (95% CI, 6.4 to 8.4 months). Median overall survival (OS) was 11.6 months (95% CI, 10.5 to 15.1 months). Hypertension ≥ grade 1 was associated with improved OS after adjusting for performance status (PS) and age (hazard ratio [HR], 0.55; 95% CI, 0.31 to 0.97; P = .04). Lower vascular endothelial growth factor levels correlated with worse PFS after adjusting for age and PS (HR, 0.90; 95% CI, 0.83 to 0.99; P = .03).
  
  
  CONCLUSIONS
  PFS and OS times were higher compared with US trials in ES-SCLC with the same chemotherapy. However, the primary end point of the trial was not met. Hypertension was associated with improved survival after adjusting for age and PS.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. ready001@mc.duke.edu
authors.forename: Neal E
authors.initials: NE
authors.lastname: Ready
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
authors.forename: Herbert H
authors.initials: HH
authors.lastname: Pang
authors.forename: Lydia D
authors.initials: LD
authors.lastname: Hodgson
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Graziano
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D016016:Proportional Hazards Models; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin