title: Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer.
abstract: OBJECTIVE
  In a phase III trial, combining bevacizumab (BV)--a recombinant, humanized, monoclonal antibody targeting vascular endothelial growth factor--with irinotecan, bolus fluorouracil (FU), and leucovorin (LV; IFL) increased survival compared with IFL alone in first-line treatment of patients with metastatic colorectal cancer (CRC). Results for the parent study of IFL/BV versus IFL/placebo are reported elsewhere. Here, we describe efficacy and safety results for the third patient cohort in this trial, who received BV combined with FU/LV, and compare them with results for concurrently enrolled patients who received IFL.
  
  
  METHODS
  Patients (N = 923) were randomly assigned to receive IFL/placebo (control), IFL/BV, or FU/LV/BV. Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA) 5 mg/kg was administered intravenously every 2 weeks. Before an interim analysis confirmed acceptable safety for IFL/BV, 313 patients were concurrently randomly assigned to these three arms; after this analysis, the FU/LV/BV arm was discontinued.
  
  
  RESULTS
  Median overall survivals were 18.3 and 15.1 months with FU/LV/BV (n = 110) and IFL/placebo (n = 100), respectively. Median progression-free survivals were 8.8 and 6.8 months, respectively. Overall response rates were 40.0% and 37.0%, and median response durations were 8.5 and 7.2 months, respectively. Adverse events consistent with those expected from FU/leucovorin- or IFL-based regimens were seen, as were modest increases in hypertension and bleeding in the bevacizumab arm, which were generally easily managed.
  
  
  CONCLUSIONS
  The FU/LV/BV regimen seems as effective as IFL and has an acceptable safety profile. FU/LV/BV is an active alternative treatment regimen for patients with previously untreated metastatic CRC.
authors.affiliation: Department of Medical Oncology and Transplantation, Room 25132, Morris Building, Box 3052, Duke University Medical Center, Durham, NC 27710, USA. hurwi004@mc.duke.edu
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: William
authors.initials: W
authors.lastname: Heim
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: Eric
authors.initials: E
authors.lastname: Holmgren
authors.forename: Julie
authors.initials: J
authors.lastname: Hambleton
authors.forename: William F
authors.initials: WF
authors.lastname: Novotny
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil