title: Histopathologic evaluation of liver metastases from colorectal cancer in patients treated with FOLFOXIRI plus bevacizumab.
abstract: BACKGROUND
  The FOLFOXIRI regimen produces a high rate of radiological and histopathological responses. Bevacizumab added to chemotherapy showed an improvement in pathological response and necrosis of colorectal liver metastases (CLMs). FOLFOXIRI plus bevacizumab produced promising early clinical results and is under investigation in several randomised trials, although no data are currently available on its effects on response of CLMs and on liver toxicities.
  
  
  METHODS
  Starting from 499 patients enrolled in first-line phase II/III trials, we selected on the basis of tissue sample availability 18 patients treated with FOLFOXIRI/XELOXIRI and 24 patients treated with FOLFOXIRI plus bevacizumab who underwent secondary resection of CLMs. The 28 untreated patients who underwent primary resection of CLMs were included as control group. Responses of CLMs and chemotherapy-induced toxicities were assessed.
  
  
  RESULTS
  Among the patients, 63% of those treated with FOLFOXIRI plus bevacizumab, as compared with 28% of those treated with only FOLFOXIRI/XELOXIRI, showed a histopathological response (P=0.033). In the two groups, 52% and 12.5%, respectively, showed necrosis ≥50% (P=0.017). The incidence of liver toxicities was not significantly increased in patients treated with FOLFOXIRI plus bevacizumab.
  
  
  CONCLUSIONS
  The addition of bevacizumab to FOLFOXIRI produces high rates of pathologic responses and necrosis of CLM without increasing liver toxicity.
authors.affiliation: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, via Roma 57, 56126 Pisa, Italy. fotiosloupakis@gmail.com
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.forename: M
authors.initials: M
authors.lastname: Schirripa
authors.forename: C
authors.initials: C
authors.lastname: Caparello
authors.forename: N
authors.initials: N
authors.lastname: Funel
authors.forename: L
authors.initials: L
authors.lastname: Pollina
authors.forename: E
authors.initials: E
authors.lastname: Vasile
authors.forename: C
authors.initials: C
authors.lastname: Cremolini
authors.forename: L
authors.initials: L
authors.lastname: Salvatore
authors.forename: M
authors.initials: M
authors.lastname: Morvillo
authors.forename: C
authors.initials: C
authors.lastname: Antoniotti
authors.forename: F
authors.initials: F
authors.lastname: Marmorino
authors.forename: G
authors.initials: G
authors.lastname: Masi
authors.forename: A
authors.initials: A
authors.lastname: Falcone
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D016022:Case-Control Studies; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin