Originally published as JCO Early Release 10.1200/JCO.2005.07.113 on June 6 2005

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Phase III Randomized Trial of FOLFIRI Versus FOLFOX4 in the Treatment of Advanced Colorectal Cancer: A Multicenter Study of the Gruppo Oncologico Dell’Italia Meridionale

From the Oncology Institute, Bari; University; La Maddalena Hospital; M. Ascoli Hospital, Palermo; Regina Elena Institute; La Sapienza University, Rome; Centro Oncologico; S. Luigi Hospital, Catania; Cardarelli Hospital, Naples; Ospedale Nord, Taranto; S. Carlo Hospital, Potenza; Cardarelli Hospital, Campobasso; G. Panico Hospital, Tricase, Italy

Address reprint requests to Giuseppe Colucci, MD, Medical and Experimental Oncology Unit, Oncology Institute, Via Amendola 209, 70126 Bari, Italy; e-mail: colucci{at}goim.it

PURPOSE: We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer.

PATIENTS AND METHODS: A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m² on day 1 with LV 100 mg/m² administered as a 2-hour infusion before FU 400 mg/m² administered as an intravenous bolus injection, and FU 600 mg/m² as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m² on day 1 with LV5FU2 regimen).

RESULTS: One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed.

CONCLUSION: There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002; and at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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