title: Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases.
abstract: OBJECTIVE
  The GONO-FOLFOXIRI regimen improved the rate of R0 secondary resection of metastases in initially unresectable metastatic colorectal cancer. The objective of this study was to evaluate the long-term outcome of resected patients and the impact of FOLFOXIRI on perioperative morbidities, mortality, and chemotherapy induced hepatotoxicity.
  
  
  METHODS
  Overall, 196 patients with initially unresectable metastatic colorectal cancer were treated with FOLFOXIRI in 2 phase II and 1 phase III trial. This regimen was associated with an elevated response rate (70.4%) and 37 patients (19%) could undergo a secondary R0 surgery on metastases. This study was registered with the Australian New Zealand Clinical Trials Registry Database at http://www.anzctr.org.au/Statistics.aspx and has ID number ACTRN12608000615381.
  
  
  RESULTS
  Main characteristics of the 37 radically resected patients were: median age 64 years (45-73), Eastern Cooperative Oncology Group Performance Status (ECOG) PS > or = 1 in 30%, synchronous metastases in 65%, multiple sites of disease in 22%, and metastases confined to the liver in 68%. Preoperative FOLFOXIRI was administered for a median of 5.5 months. There was no perioperative mortality and all morbidities (27% of patients) resolved without sequelae. After a median follow up of 67 months, 5-year and 8-year survival are 42% and 33% respectively. At 5 years, 29% of patients are free of disease. The analysis of treatment-induced liver injury showed neither G3 vascular toxicity nor G4 steatosis, and steato-hepatitis in only 5% of patients.
  
  
  CONCLUSIONS
  The GONO-FOLFOXIRI regimen allow an R0 surgery in approximately 1 out of 5 unselected patients with initially unresectable metastatic colorectal cancer, and the long-term survival of resected patients is considerable. Neoadjuvant FOLFOXIRI for 3-6 months is safe and not associated with severe liver injury.
authors.affiliation: Unità Operativa Oncologia Medica, Azienda USL-6, Istituto Toscano Tumori, Livorno, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.forename: Luca
authors.initials: L
authors.lastname: Pollina
authors.forename: Enrico
authors.initials: E
authors.lastname: Vasile
authors.forename: Samanta
authors.initials: S
authors.lastname: Cupini
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.forename: Isa Maura
authors.initials: IM
authors.lastname: Brunetti
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Naso
authors.forename: Franco
authors.initials: F
authors.lastname: Filipponi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pietrabissa
authors.forename: Orlando
authors.initials: O
authors.lastname: Goletti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Baldi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fornaro
authors.forename: Michele
authors.initials: M
authors.lastname: Andreuccetti
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006498:Hepatectomy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011013:Pneumonectomy; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin