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

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.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).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-FU2 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).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.