title: A phase II study of capecitabine, oxaliplatin, bevacizumab and cetuximab in the treatment of metastatic colorectal cancer.
abstract: OBJECTIVE
  This study was designed to determine the efficacy and tolerability of capecitabine, oxaliplatin and bevacizumab in combination with cetuximab as first-line therapy for advanced colorectal cancer.
  
  
  METHODS
  Patients with previously untreated advanced colorectal cancer received oxaliplatin 130 mg/m² and bevacizumab 7.5 mg/kg every three weeks, capecitabine 850 mg/m² twice daily on days 1-14, and cetuximab at 400 mg/m² load and 250 mg/m² weekly. KRAS, BRAF and PI3K mutation status from paraffin-embedded tumor samples were assessed using real-time polymerase chain reaction.
  
  
  RESULTS
  Thirty patients were evaluable for safety and efficacy. One patient had a complete response and 12 patients had a partial response, giving an overall response rate of 43% (95% confidence interval (CI) 25%-63%). Fifteen patients had stable disease. The median time to progression was 10.3 months (95% CI, 6.8-16.3 months). The median overall survival was 18.8 months (95% CI, 14.2-23.7 months). Common grade ≥ 3 non-hematological toxicities were skin rash (37%), sensory neuropathy (27%) and diarrhea (17%). Grade ≥ 3 hematological toxicities were uncommon. Mutations in KRAS, BRAF and PI3K occurred in 34.5%, 10.3% and 10.3% of patients respectively, but did not correlate with treatment outcome.
  
  
  CONCLUSIONS
  The addition of cetuximab to capecitabine, oxaliplatin and bevacizumab did not improve the three-drug regimen activity compared to published data and was associated with significant toxicities requiring frequent dose modifications. KRAS, BRAF, and PI3K mutation status were consistent with published literature, but did not affect outcome in this small study.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Nan Soon
authors.initials: NS
authors.lastname: Wong
authors.forename: Nishan H
authors.initials: NH
authors.lastname: Fernando
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Nixon
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cushman
authors.forename: Mebea
authors.initials: M
authors.lastname: Aklilu
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Blobe
authors.forename: Jill
authors.initials: J
authors.lastname: Ashton
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D019869:Phosphatidylinositol 3-Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil