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(Date reviewed: 12/12/2003) - For many years the standard therapy for metastatic colorectal cancer has been 5-fluouracil (5-FU) and leucovorin. Now a large randomized clinical trial has shown that adding irinotecan (CPT-11) to this standard regimen results in higher rates of tumor shrinkage, a longer time to disease progression, and longer overall survival compared to the use of 5-FU and leucovorin alone. The results appear in the Sept. 28, 2000, issue of the New England Journal of Medicine (see the journal abstract).

Led by Leonard B. Saltz, M.D. at Memorial Sloan Kettering Cancer Center in New York City, the trial included 683 patients who were assigned randomly to one of three arms. Patients on one of the arms received 5-FU and leucovorin alone, those on a second arm received irinotecan alone, and those on the third arm received all three drugs.

Irinotecan alone showed no benefit compared to 5-FU and leucovorin, but the three-drug combination nearly doubled tumor response rate compared to the standard therapy (39 percent versus 21 percent). The time to disease progression was 7 months in the irinotecan combination arm compared to 4.3 months in the 5FU/leucovorin arm, and the median survival time was 14.8 months compared to 12.6 months. The incidence of serious side effects was no higher in the irinotecan combination arm than in the 5-FU/leucovorin arm.

Irinotecan was approved by the U.S. Food and Drug Administration for colorectal cancer in 1996 as a second line therapy -- that is, for use after 5-FU treatment had failed. This spring, the FDA also approved it as first-line therapy, based partly on the results of this study. Other trials are now looking at the new drug in patients with less advanced colorectal cancer.

For example, one large current trial, involving several of the National Cancer Institute's cooperative clinical trials groups, is enrolling patients with locally advanced, locally recurrent, or metastatic disease. It is comparing the combination used in this trial - irinotecan/5-FU/leucovorin -- to two other combinations - oxaliplatin/5-FU/leucovorin/ and irinotecan/oxaliplatin. Oxaliplatin is another new drug that has shown promise in earlier trials. [Editor's note (06/04/01): This trial, N9741, as well as a second trial involving irinotecan, CLB 89803, are temporarily suspended.]