title: Neoadjuvant FOLFIRI+bevacizumab in patients with resectable liver metastases from colorectal cancer: a phase 2 trial.
abstract: BACKGROUND
  Preoperative treatment of resectable liver metastases from colorectal cancer (CRC) is a matter of debate. The aim of this study was to assess the feasibility and activity of bevacizumab plus FOLFIRI in this setting.
  
  
  METHODS
  Patients aged 18-75 years, PS 0-1, with resectable liver-confined metastases from CRC were eligible. They received bevacizumab 5 mg kg(-1) followed by irinotecan 180 mg m(-)(2), leucovorin 200 mg m(-)(2), 5-fluorouracil 400 mg m(-)(2) bolus and 5-fluorouracil 2400 mg m(-)(2) 46-h infusion, biweekly, for 7 cycles. Bevacizumab was stopped at cycle 6. A single-stage, single-arm phase 2 study design was applied with 1-year progression-free rate as the primary end point, and 39 patients required.
  
  
  RESULTS
  From October 2007 to December 2009, 39 patients were enrolled in a single institution. Objective response rate was 66.7% (95% exact CI: 49.8-80.9). Of these, 37 patients (94.9%) underwent surgery, with a R0 rate of 84.6%. Five patients had a pathological complete remission (14%). Out of 37 patients, 16 (43.2%) had at least one surgical complication (most frequently biloma). At 1 year of follow-up, 24 patients were alive and free from disease progression (61.6%, 95% CI: 44.6-76.6). Median PFS and OS were 14 (95% CI: 11-24) and 38 (95% CI: 28-NA) months, respectively.
  
  
  CONCLUSIONS
  Preoperative treatment of patients with resectable liver metastases from CRC with bevacizumab plus FOLFIRI is feasible, but further studies are needed to define its clinical relevance.
authors.affiliation: Medical Oncology, Abdominal Department, National Cancer Institute G. Pascale Foundation, Via Mariano Semmola, 80131 Napoli, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Nasti
authors.forename: M C
authors.initials: MC
authors.lastname: Piccirillo
authors.forename: F
authors.initials: F
authors.lastname: Izzo
authors.forename: A
authors.initials: A
authors.lastname: Ottaiano
authors.forename: V
authors.initials: V
authors.lastname: Albino
authors.forename: P
authors.initials: P
authors.lastname: Delrio
authors.forename: C
authors.initials: C
authors.lastname: Romano
authors.forename: P
authors.initials: P
authors.lastname: Giordano
authors.forename: S
authors.initials: S
authors.lastname: Lastoria
authors.forename: C
authors.initials: C
authors.lastname: Caracò
authors.forename: E
authors.initials: E
authors.lastname: de Lutio di Castelguidone
authors.forename: R
authors.initials: R
authors.lastname: Palaia
authors.forename: G
authors.initials: G
authors.lastname: Daniele
authors.forename: L
authors.initials: L
authors.lastname: Aloj
authors.forename: G
authors.initials: G
authors.lastname: Romano
authors.forename: R V
authors.initials: RV
authors.lastname: Iaffaioli
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; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
references.citation: Oncology. 2010;78(5-6):329-39
references.pmid: 20733336
references.citation: J Clin Oncol. 2008 Apr 10;26(11):1830-5
references.pmid: 18398148
references.citation: Lancet Oncol. 2010 Jan;11(1):38-47
references.pmid: 19942479
references.citation: N Engl J Med. 2009 Apr 2;360(14):1408-17
references.pmid: 19339720
references.citation: J Clin Oncol. 2005 Aug 1;23(22):4853-5
references.pmid: 16051943
references.citation: Ann Oncol. 2009 Nov;20(11):1842-7
references.pmid: 19406901
references.citation: J Clin Oncol. 2006 May 1;24(13):2065-72
references.pmid: 16648507
references.citation: Eur J Cancer. 2006 Sep;42(14):2212-21
references.pmid: 16904315
references.citation: Ann Surg. 2010 Jul;252(1):124-30
references.pmid: 20562613
references.citation: Br J Cancer. 2011 Mar 29;104(7):1079-84
references.pmid: 21386839
references.citation: Ann Surg. 2004 Dec;240(6):1052-61; discussion 1061-4
references.pmid: 15570210
references.citation: CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29
references.pmid: 14974761
references.citation: N Engl J Med. 2004 Jun 3;350(23):2335-42
references.pmid: 15175435
references.citation: Lancet. 2008 Mar 22;371(9617):1007-16
references.pmid: 18358928
references.citation: J Clin Oncol. 2008 Apr 20;26(12):2013-9
references.pmid: 18421054
references.citation: Cancer. 1994 Jun 1;73(11):2680-6
references.pmid: 8194005