Death rate sparks concern over colon cancer drug

By Elizabeth Cohen
CNN Medical Unit

ATLANTA (CNN) -- Patients taking a commonly prescribed treatment for colon cancer died at almost three times the rate of patients who took other drugs for the same disease, said a biostatistician for the Mayo Clinic Thursday.

"It raised the death rate to what we considered an unacceptable rate," said Daniel Sargent, the biostatistician who is the lead author of a letter to be published on the matter in an upcoming issue of the New England Journal of Medicine.

As a result, doctors involved in a multi-center trial of the drug will give it in lower doses and be more aggressive about looking out for warning signs of toxicity, he said.

The manufacturer has sent an advisory notice to doctors.

In the first two months of receiving the chemotherapy drug irinotecan, 33 out of 1,199 patients died. Among the patients who took other chemotherapy drugs, 10 out of 905 patients died within the same period.

"This is obviously a situation we're quite concerned about," said Dr. Leonard Saltz, a researcher at Memorial Sloan-Kettering Cancer Center, who conducted one of the two studies on irinotecan, which is manufactured by Pharmacia and sold under the brand name Camptosar.

Studies show that the drug, which has been on the market since 1998, increases life expectancy by about two months for patients with advanced colorectal cancer.

A spokesman for Pharmacia called the death-rate findings "preliminary" and "not statistically significant." But he added that the company is concerned and sent out letters to doctors last week advising them about the results.

Dr. Ivan Horak, Pharmacia's vice president for clinical oncology research and development, said more than 15,000 cancer patients have taken the drug and the increased death rate had not been seen before.

Dr. Michael O'Connell, deputy director for clinical affairs at the Mayo Clinic Cancer Center in Rochester, Minnesota, said the deaths were spread out among different medical centers that pooled their data and may not have been obvious to individual physicians.

"If you're a doctor practicing on your own, you might only see one, or maybe two deaths," said O'Connell.

O'Connell said doctors in the study will now give Camptosar in lower doses, and be more aggressive about looking out for warning signs of toxicity, including diarrhea, nausea, vomiting, and a low white blood cell count.

He added that his group is investigating why some people had toxic reactions to Camptosar but not others. "There seems to be a small subset of people who are exquisitely sensitive," he said.

Camptosar is one of Pharmacia's fastest-growing drugs. According to the company, the drug had $137 million in sales in the first quarter of 2001 -- a 72 percent increase over the first quarter of last year.

The report about death rates has highlighted a disagreement among oncologists. Some give Camptosar just to patients whose colon cancer has spread to other parts of the body. Others give it much earlier -- as a first-line treatment for people whose cancer has not spread.

According to Pharmacia, first-line use now accounts for more than half of sales, but Dr. O'Connell said because of toxicity concerns he won't use it as a first-line treatment.

Dr. Saltz, at Memorial Sloan-Kettering, said he only uses it as first-line therapy when the patient is part of an experimental study. "I've been saying anytime anyone will listen, this is still under study and until we know the answer it shouldn't be standard therapy" as a first-line treatment.