Annals of Surgery

Skip Navigation LinksHome > March 2009 - Volume 249 - Issue 3 > Long-Term Outcome of Initially Unresectable Metastatic Color...
Annals of Surgery:
doi: 10.1097/SLA.0b013e31819a0486
Original Articles

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

Masi, Gianluca MD*; Loupakis, Fotios MD*; Pollina, Luca MD†††; Vasile, Enrico MD*; Cupini, Samanta MD*; Ricci, Sergio MD‡; Brunetti, Isa Maura MD‡; Ferraldeschi, Roberta MD§; Naso, Giuseppe MD§; Filipponi, Franco MD¶††; Pietrabissa, Andrea MD∥††; Goletti, Orlando MD**††; Baldi, Giacomo MD*; Fornaro, Lorenzo MD*; Andreuccetti, Michele CTA*; Falcone, Alfredo MD*††

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Objective/Background: 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.

Patients and 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 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 ≥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.

© 2009 Lippincott Williams & Wilkins, Inc.


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