The final version of the letter will be published on June 21.
The authors have reported an unexpectedly high rate of death associated with the combination of irinotecan, fluorouracil, and leucovorin, used for treatment of colorectal cancer, in two separate studies.
Both trials are currently being performed throughout the United States and Canada.
The first study is being conducted on patients with metastatic colon cancer. In this trial, the regimen of irinotecan, fluorouracil, and leucovorin is being compared with a regimen of oxaliplatin, fluorouracil, and leucovorin, and a regimen of oxaliplatin and irinotecan.
12 of the 14 deaths in the group assigned to the regimen of irinotecan, fluorouracil, and leucovorin had several characteristics in common. These were dehydration (resulting from diarrhea, nausea, and vomiting), neutropenia, and sepsis, leading to death.
13 of the 14 deaths were found to occur during the first 6-week cycle of chemotherapy or immediately afterward.
The second adjuvant study involving patients with resected stage III colon cancer, is comparing fluorouracil and leucovorin with the irinotecan, fluorouracil, and leucovorin regimen.
14 deaths have been reported in the group assigned to receive triple therapy. The causes of these were pulmonary emboli (in 3 patients); sepsis (3); aspiration (3); myocardial infarction (1); dehydration and neutropenia (1); a cerebrovascular accident (1); bowel ischemia, infarct, or both (1); and unknown (1).
|Clinical factors that increase mortality risk from the regimen have not been identified.|
|N Engl J Med|
On the basis of these data the researchers have recommended the suspension of both trials.
In each trial, dose modifications were made in an attempt to ameliorate the toxic effects of the regimen.
Daniel J. Sargent, of the Mayo Clinic, Rochester, Minnesota, and fellow authors comment, "Vigilant monitoring of all patients who are receiving this combination of irinotecan, fluorouracil, and leucovorin is called for because specific clinical factors that increase the risk of adverse effects have not yet been identified."
"The regimen has been shown to improve survival in patients with advanced colorectal cancer. Combination therapy with irinotecan, fluorouracil, and leucovorin should continue to be an option in this treatment setting, but in our experience has been associated with an excessive rate of early deaths," they conclude.
Patients concerned about these findings will be reading further reports from CNN, MSNBC, and the Washington Post.