Colon Cancer Treatment May Be More Toxic Than Thought
May 17, 2001 -- The newest front-line treatment for patients with advanced colon cancer, approved by the FDA just over a year ago, may be more toxic than previously believed.
According to a letter to the editor that was slated to appear in the June 21 issue of The New England Journal of Medicine, two separate studies show a chemotherapy regimen combining the recently approved Camptosar with two well-known drugs -- 5-FU and Leucovorin -- caused an unexpectedly high number of deaths within 60 days of starting treatment. The medical journal is releasing the letter in advance "because of its potential importance in the treatment of colorectal cancer."
"We wanted doctors in the country to realize that there are a few patients that are particularly sensitive to this chemotherapy regimen and that they need to exercise particular caution when they use this drug combination," letter author Michael O'Connell, MD, tells WebMD. O'Connell is a deputy director of the Mayo Clinic Cancer Center in Rochester, Minn. He also chairs the North Central Cancer Treatment Group, a cooperative group of medical institutions that work together on clinical trials.
In the letter, O'Connell and three other researchers write that in the North Central Cancer Treatment Group trial, 14 colon cancer patients who received the three-drug combination died, compared with five patients in each of two other medication arms. In the second trial, by the Cancer and Leukemia Group B cooperative group, 14 patients who received the triple combination died, compared with five patients in another medication group.
New patient enrollment in the two trials, both sponsored by the National Cancer Institute, has been suspended, and patients receiving the triple-drug combination have had their medication doses modified to reduce the toxic effects of the treatment.
The number of deaths in the Camptosar-5-FU-Leucovorin combination groups come as a bit of a surprise: An earlier study, also published in The New England Journal of Medicine, reported the regimen was not associated with a significant increase in toxicity when compared with two other chemotherapy regimens for colon cancer. Approximately 15,000 patients have been treated with the combination.
"I would have to say that we were surprised," says O'Connell. "We think that the higher-than-expected death rates maybe due to the fact that we had a lot more patients included in the trials -- there were nearly 2,100 patients in these trials, whereas the original study had approximately 680 patients in it." The larger number of participants "may have allowed us to identify more precisely this relatively uncommon but very serious early toxic reaction: the early death."
Cancer expert Leonard Saltz, MD, says that the way these deaths were identified so quickly shows that the system is working. "The safety system we have in the cooperative groups ... is a system where the data is monitored carefully to look for unexpected developments," he says. "When you have such a serious unexpected event as early death, to pick that up at a very early level allows us to put the breaks on, stop and think, and protect the people involved in the study. That is what happened here." Saltz, an associate attending physician at New York's Memorial Sloan-Kettering Cancer Center, is the lead investigator in the Cancer and Leukemia Group B trial.