The role of 5-fluorouracil (5-FU) reintroduction with irinotecan or oxaliplatin in truly 5-FU-refractory advanced colorectal cancer patients.

Objectives: Although several evidences have demonstrated a synergistic activity of 5-fluorouracil with irinotecan and oxaliplatin, thus explaining the use of this drug combination in the first-line treatment of advanced colorectal cancer, the need for the reintroduction of 5-FU in the second-line setting is more questionable. Methods: We retrospectively evaluated the outcome of patients developing progressive disease while on an infusional 5-FU-based front-line chemotherapy and subsequently treated with one of the four following chemotherapy regimens: irinotecan, oxaliplatin and irinotecan or oxaliplatin both combined with the de Gramont schedule (LV5-FU2). Results: 225 patients (137 males and 88 females), were eligible for analysis. Second-line chemotherapy consisted of irinotecan in 79 patients (35%, group A), oxaliplatin in 47 patients (21%, group B), irinotecan with LV5+U2 in 53 patients (24%, group C) and oxaliplatin with LV5-FU2 in the remaining 46 cases (20%, group D). The response rate to second-line chemotherapy was obtained in 6/79 patients (8%) in group A, in 4/47 patients(9%) in group B, in 11/53 patients (21%) in group C and in 10/46 patients (22%) in group D (p=0.04). Conclusions: These data suggest that reintroduction of 5-FU could increase irinotecan and oxaliplatin activity in patients progressing during a 5-FU-based first-line chemotherapy. Copyright (C) 2005 S. Karger AG, Basel.