Irinotecan/Fluorouracil/Leucovorin or the Same Regimen Followed by Oxaliplatin/Fluorouracil/Leucovorin in Metastatic Colorectal Cancer

Background: This study reports the long-term follow-up of patients with metastatic colorectal cancer (CRC) participating in a randomised phase II study that compared the efficacy and toxicity of the combination of irinotecan (IRI), fluorouracil (FU) with leucovorin (LV) (arm A) versus sequential chemotherapy with IRI plus FU/LV followed by oxaliplatin (OXA) plus FU/LV (arm B) as first line therapy. Materials and Methods: Intent-to-treat analysis was performed on 417 patients (211 in arm A and 206 in arm B). Treatment schedules of weekly IRI 80 mg/m 2 or OXA 45 mg/m 2 plus LV 200 mg/m 2 immediately followed by intravenous bolus FU 450 mg/m 2 for 6 weeks were followed by a 2-week rest period. Treatment continued for 4 cycles. Patients in arm A were treated with IRI/FU/LV for 4 cycles, while patients in arm B were initially treated with IRI/FU/LV for 2 cycles followed by sequential administration of 2 cycles of OXA/FU/LV. Results: No significant difference emerged in overall response rate or overall survival. There was a difference in progression-free survival (median, 7.3 versus 8.2 months, p=0.040) in favour of arm B. Toxicity profiles were similar in both arms. Conclusion: IRI/FU/LV and IRI/FU/LV followed by OXA/FU/LV showed comparable activity with a manageable toxicity profile. Colorectal cancer (CRC) is a worldwide public health problem, accounting for nearly 800,000 new cases diagnosed each year and approximately 500,000 deaths (1). Significant advances have been made in the management options for patients with metastatic disease and a median survival of 21- 24 months is now frequently reported. Over the past 10 years, three new chemotherapeutic agents have been approved for metastatic CRC. These compounds