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 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 ≥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.
We evaluated 196 patients with initially unresectable metastatic colorectal cancer treated with the triple drug combination FOLFOXIRI. This regimen allowed an R0 surgery in approximately 1/5 patients, and the long-term outcome of resected patients is considerable (8-year survival 33%). Neoadjuvant FOLFOXIRI for 3–6 months is safe and not associated with severe liver injury.
From the *Unità Operativa Oncologia Medica, Azienda USL-6, Istituto Toscano Tumori, Livorno, Italy; †Unità Operativa Anatomia e Istologia Patologica I, Azienda Ospedaliero-Universitaria, Istituto Toscano Tumori, Pisa, Italy; ‡Unità Operativa Oncologia Medica, Azienda Ospedaliero-Universitaria, Istituto Toscano Tumori, Pisa, Italy; §Unità Operativa Oncologia Medica B, Dipartimento di Medicina Sperimentale, Università la Sapienza, Roma, Italy; ¶Unità Operativa Chirurgia Generale e Trapianto Fegato Universitaria, Azienda Ospedaliero-Universitaria, Istituto Toscano Tumori, Pisa, Italy; ∥Unità Operativa Chirurgia Generale I Universitaria, Azienda Ospedaliero-Universitaria, Istituto Toscano Tumori, Pisa, Italy; **Unità Operativa Chirurgia Generale, Azienda USL-5, Istituto Toscano Tumori, Pisa, Italy; and ††Dipartimento di Oncologia, dei Trapianti e Nuove Tecnologie in Medicina, Università degli Studi, Pisa, Italy.
Acknowledgements of research support: Supported in part by a research grant of the Associazione Italiana Ricerca Cancro (A.I.R.C.) and by the Fondazione A.R.C.O.
Correspondence and requests for reprints to: Prof. Alfredo Falcone, Department of Oncology, Transplants and New Techologies in Medicine, University of Pisa, Department of Oncology, Azienda USL-6 of Livorno, Viale Alfieri, 36, 57124 Livorno, Italy, Phone +39 0586 223189, Fax +39 0586 223457, E-mail: email@example.com.