title: Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.
  
  
  METHODS
  Patients with metastatic colorectal cancer who had progressed on therapy with 5-FU, oxaliplatin and irinotecan in the first and second line setting and on the combination of irinotecan and cetuximab in third line setting independent of their KRAS mutation status, were treated with irinotecan and cetuximab combined with bevacizumab in a dosage of 5 mg/kg. All drugs were administered every second week.
  
  
  RESULTS
  From January 2007 to November 2008 27 patients were treated with cetuximab, irinotecan and bevacizumab. The triple-combination was well tolerated. Progression free survival (PFS) was 8.3 months and median overall survival (mOS) was 12.0 months. Two patients without KRAS mutation (7%) obtained a partial response and 17 (63%) had stable disease for at least two months. A retrospective KRAS mutation analysis revealed that there was a trend toward longer PFS and mOS in patients without KRAS mutations compared to patients with KRAS mutations with a PFS of 8.9 vs. 5.1 months and a mOS of 12.7 vs. 9.0 months.
  
  
  CONCLUSIONS
  Bevacizumab is safe to add to irinotecan and cetuximab with a toxicity profile that seems to be similar to what would be expected from the agents alone. The results indicate that adding bevacizumab to irinotecan and cetuximab in a fourth line setting may induce a high rate of disease control in heavily pretreated patients with metastatic colorectal cancer.
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark. olelar02@heh.regionh.dk
authors.forename: Finn Ole
authors.initials: FO
authors.lastname: Larsen
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.forename: Dorte
authors.initials: D
authors.lastname: Nielsen
authors.forename: Kristin
authors.initials: K
authors.lastname: Skougaard
authors.forename: Camilla
authors.initials: C
authors.lastname: Qvortrup
authors.forename: Kirsten
authors.initials: K
authors.lastname: Vistisen
authors.forename: Anne-Lene
authors.initials: AL
authors.lastname: Fromm
authors.forename: Trine L
authors.initials: TL
authors.lastname: Jørgensen
authors.forename: Jon K
authors.initials: JK
authors.lastname: Bjerregaard
authors.forename: Estrid
authors.initials: E
authors.lastname: Hoegdall
authors.forename: Benny V
authors.initials: BV
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000068258:Bevacizumab; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin