title: Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.
abstract: BACKGROUND
  Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer.
  
  
  METHODS
  We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome.
  
  
  RESULTS
  The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group.
  
  
  CONCLUSIONS
  The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.)
authors.affiliation: Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Jolien
authors.initials: J
authors.lastname: Tol
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.forename: Annemieke
authors.initials: A
authors.lastname: Cats
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Rodenburg
authors.forename: Geert J M
authors.initials: GJ
authors.lastname: Creemers
authors.forename: Jolanda G
authors.initials: JG
authors.lastname: Schrama
authors.forename: Frans L G
authors.initials: FL
authors.lastname: Erdkamp
authors.forename: Allert H
authors.initials: AH
authors.lastname: Vos
authors.forename: Cees J
authors.initials: CJ
authors.lastname: van Groeningen
authors.forename: Harm A M
authors.initials: HA
authors.lastname: Sinnige
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Richel
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
authors.forename: Jeroen R
authors.initials: JR
authors.lastname: Dijkstra
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Vink-Börger
authors.forename: Ninja F
authors.initials: NF
authors.lastname: Antonini
authors.forename: Linda
authors.initials: L
authors.lastname: Mol
authors.forename: Johan H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Otilia
authors.initials: O
authors.lastname: Dalesio
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; 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; D000069287:Capecitabine; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011788:Quality of Life; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil