title: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
abstract: BACKGROUND
  Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy.
  
  
  METHODS
  Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life.
  
  
  RESULTS
  The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progression-free survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed.
  
  
  CONCLUSIONS
  The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
authors.affiliation: Duke University, Durham, NC, USA. hurwi004@mc.duke.edu
authors.forename: Herbert
authors.initials: H
authors.lastname: Hurwitz
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: William
authors.initials: W
authors.lastname: Novotny
authors.forename: Thomas
authors.initials: T
authors.lastname: Cartwright
authors.forename: John
authors.initials: J
authors.lastname: Hainsworth
authors.forename: William
authors.initials: W
authors.lastname: Heim
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: Ari
authors.initials: A
authors.lastname: Baron
authors.forename: Susan
authors.initials: S
authors.lastname: Griffing
authors.forename: Eric
authors.initials: E
authors.lastname: Holmgren
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
authors.forename: Gwen
authors.initials: G
authors.lastname: Fyfe
authors.forename: Beth
authors.initials: B
authors.lastname: Rogers
authors.forename: Robert
authors.initials: R
authors.lastname: Ross
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; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011788:Quality of Life; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin