title: Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial.
abstract: OBJECTIVE
  Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, increases survival when combined with irinotecan-based chemotherapy in first-line treatment of metastatic colorectal cancer (CRC). This randomized, phase II trial compared bevacizumab plus fluorouracil and leucovorin (FU/LV) versus placebo plus FU/LV as first-line therapy in patients considered nonoptimal candidates for first-line irinotecan.
  
  
  METHODS
  Patients had metastatic CRC and one of the following characteristics: age > or = 65 years, Eastern Cooperative Oncology Group performance status 1 or 2, serum albumin < or = 3.5 g/dL, or prior abdominal/pelvic radiotherapy. Patients were randomly assigned to FU/LV/placebo (n = 105) or FU/LV/bevacizumab (n = 104). The primary end point was overall survival. Secondary end points were progression-free survival, response rate, response duration, and quality of life. Safety was also assessed.
  
  
  RESULTS
  Median survival was 16.6 months for the FU/LV/bevacizumab group and 12.9 months for the FU/LV/placebo group (hazard ratio, 0.79; P = .16). Median progression-free survival was 9.2 months (FU/LV/bevacizumab) and 5.5 months (FU/LV/placebo); hazard ratio was 0.50; P = .0002. Response rates were 26.0% (FU/LV/bevacizumab) and 15.2% (FU/LV/placebo) (P = .055); duration of response was 9.2 months (FU/LV/bevacizumab) and 6.8 months (FU/LV/placebo); hazard ratio was 0.42; P = .088. Grade 3 hypertension was more common with bevacizumab treatment (16% v 3%) but was controlled with oral medication and did not cause study drug discontinuation.
  
  
  CONCLUSIONS
  Addition of bevacizumab to FU/LV as first-line therapy in CRC patients who were not considered optimal candidates for first-line irinotecan treatment provided clinically significant patient benefit, including statistically significant improvement in progression-free survival.
authors.affiliation: Division of Hematology/Oncology, UCLA School of Medicine, 10945 LeConte Ave, Suite 2338J, Los Angeles, CA 90095-7187, USA. fkabbina@mednet.ucla.edu
authors.forename: Fairooz F
authors.initials: FF
authors.lastname: Kabbinavar
authors.forename: Joseph
authors.initials: J
authors.lastname: Schulz
authors.forename: Michael
authors.initials: M
authors.lastname: McCleod
authors.forename: Taral
authors.initials: T
authors.lastname: Patel
authors.forename: John T
authors.initials: JT
authors.lastname: Hamm
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.forename: Robert
authors.initials: R
authors.lastname: Mass
authors.forename: Brent
authors.initials: B
authors.lastname: Perrou
authors.forename: Betty
authors.initials: B
authors.lastname: Nelson
authors.forename: William F
authors.initials: WF
authors.lastname: Novotny
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D010919:Placebos; D011788:Quality of Life; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin