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Irinotecan Not Effective in Adjuvant Therapy for Colon Cancer Adapted from the NCI Cancer Bulletin, vol. 4/no. 24, August 21, 2007 (see the current issue). Final results from a Cancer and Leukemia Group B (CALGB) trial show that irinotecan should not be added to 5-fluorouracil (5-FU) and leucovorin in the adjuvant treatment of stage III colon cancer. In the CALGB 89803 trial, led by Dr. Leonard B. Saltz and colleagues at Memorial Sloan-Kettering Cancer Center (see the protocol summary), no survival benefit was seen in the adjuvant setting. These results appear in the August 10, 2007, Journal of Clinical Oncology (see the journal abstract). "These results were unexpected," writes Dr. Neal Meropol of the Fox Chase Cancer Center in Philadelphia in a related editorial. "After all, CPT 11 [irinotecan] had previously shown clear activity in patients with metastatic cancer - the accepted proving ground for subsequent adjuvant therapies."
In previous trials, Dr. Saltz and others had found that adding irinotecan to 5-FU and leucovorin provided a modest but statistically significant improvement in survival compared to treatment with 5-FU and leucovorin alone in patients with metastatic colon cancer. Based on these findings, it was anticipated that the three-drug combination would also be effective when given after surgery to patients with less advanced disease.
"The report by Saltz et al. sends a strong message," said Meropol. "Randomized trials are necessary to prove the obvious, [because] history tells us that the obvious is often disproved."
Saltz and colleagues agreed. "The results of our trial demonstrate the dangers of jumping to conclusions before completion of the formal clinical trial assessment." In addition, combining irinotecan with 5-FU and leucovorin significantly increased treatment toxicity, including greater reductions in white blood cell counts and increases in infection, vomiting, and fatigue. More than 10 percent (65) of the 635 patients assigned to the irinotecan-containing arm had their treatment stopped because of an adverse event. Another 82 patients receiving the three-drug combination withdrew from the trial, more than twice the number of patients who withdrew from the 5-FU plus leucovorin arm. Within 60 days of entering the study, 14 patients receiving irinotecan died, compared to five in the 5-FU and leucovorin arm.
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