Triplet Combination of Fluoropyrimidines, Oxaliplatin, and Irinotecan in the First-Line Treatment of Metastatic Colorectal Cancer

In recent years, the treatment of metastatic colorectal cancer has improved because of the availability of 3 active cytotoxic drugs, 2 monoclonal antibodies, and the expanded use of surgery on metastases in selected patients, leading to a median overall survival of almost 2 years. Chemotherapy remains the primary option for these patients, and the development of first-line chemotherapy regimens associated with higher activity and improved efficacy is still a major topic of interest. This article provides an overview of the development of a first-line treatment combination of irinotecan and oxaliplatin plus 5-fluorouracil (5-FU; FOLFOXIRI) or oral fluoropyrimidines in patients with metastatic colorectal cancer, evaluating the feasibility and the activity of these regimens in phase I/II studies and the results of a recent phase III study that demonstrates that FOLFOXIRI significantly increases response rate, radical surgical resection of metastases, progression-free survival, and overall survival compared with an infusional 5-FU–containing doublet such as FOLFIRI (5-FU/leucovorin/irinotecan).