Irinotecan and high-dose fluorouracil/leucovorin for metastatic colorectal cancer.

Two randomized phase III trials with irinotecan as second-line treatment of metastatic colorectal cancer have shown that irinotecan (CPT-11, Camptosar) significantly improves survival when compared with best supportive care or continuous infusion of fluorouracil (5-FU) after failure of 5-FU. The combination of irinotecan and 5-FU/leucovorin produced a significantly higher response rate (40.8% vs 23.1%, P < .001), longer time to progression of disease (6.7 vs 4.4 months, P < .001), longer median survival (17.4 vs 14.1 months, P = .03), and a greater chance of survival at 1 year (69% vs 59%, P = .03) than 5-FU/leucovorin treatment alone. Such benefits have not previously been demonstrated in this setting. Although the use of irinotecan in combination with 5-FU/leucovorin increased the likelihood of neutropenia, the incidence of febrile neutropenia and infection remained low. Other toxic effects were manageable, noncumulative, and reversible.