title: Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases.
abstract: BACKGROUND
  The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM.
  
  
  METHODS
  A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1-8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared.
  
  
  RESULTS
  Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency (P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups.
  
  
  CONCLUSIONS
  Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.
authors.affiliation: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kishi
authors.forename: Daria
authors.initials: D
authors.lastname: Zorzi
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Contreras
authors.forename: Dipen M
authors.initials: DM
authors.lastname: Maru
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
authors.forename: Dario
authors.initials: D
authors.lastname: Ribero
authors.forename: Manuela
authors.initials: M
authors.lastname: Motta
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ravarino
authors.forename: Mauro
authors.initials: M
authors.lastname: Risio
authors.forename: Steven A
authors.initials: SA
authors.lastname: Curley
authors.forename: Eddie K
authors.initials: EK
authors.lastname: Abdalla
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
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 / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006498:Hepatectomy; D048550:Hepatic Insufficiency / Q000139:chemically induced*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011300:Preoperative Care; D012074:Remission Induction
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil