Cancer drug tests stopped over toxicity findings

The Associated Press
Friday May 18, 2001

BOSTON — Two national studies of a widely used drug for colorectal cancer were suspended for new patients because the drug turned out to be more toxic than expected. 

Some doctors have viewed the five-year-old drug irinotecan, also known by the brand name Camptosar, as the most useful drug against advanced colorectal cancer in years.  

It is recommended as standard therapy in combination with other drugs. 

However, almost three times as many patients died taking the standard drug combination in the latest studies sponsored by the National Cancer Institute. 

The researchers reported their findings in a letter to the editor of The New England Journal of Medicine. Prompted by the urgency of the findings, the journal released the letter Thursday, although it is scheduled for publication June 21. 

In one study of 841 patients, the investigators tested irinotecan, as it is now approved for use, on advanced patients whose cancer has spread to other organs. In the other study of 1,263 so-called stage III patients, it had not yet spread.  

The patients came from across the United States and Canada. 

In each study, 14 patients died after they were given a standard drug combination with irinotecan. Just five died with other drug combinations in each study. 

Some of the dead patients had blood clots, blood poisoning, dehydrating diarrhea, or a drop in white blood cells.  

The investigators said it is not yet clear why certain patients suffered such effects. The researchers will review their findings in coming months for clues. 

The study of the advanced patients may resume within weeks with new patients on lower doses. The other study was reaching its target number of patients just as the toxicity data arose, so it won’t reopen. 

One of the study chairmen, Dr. Michael O’Connell, of the Mayo Clinic in Rochester, Minn., recommended that doctors in the field reduce the drug’s dose and watch more carefully for signs of toxicity. 

However, he and others said earlier studies prove the drug can prolong life in advanced cases – though for a limited time.  

“Irinotecan remains an important drug,” said the lead investigator of the stage III study, Dr. Leonard Saltz, of Memorial Sloan-Kettering Cancer Center in New York City. 

Colorectal cancer – cancer of the colon and rectum – is America’s No. 2 cancer killer after lung cancer, claiming about 56,000 lives annually. 

About 15,000 patients with advanced colorectal cancer have been treated with the drug since it was approved as a first-line treatment last year, according to maker Pharmacia & Upjohn. Previously, it was used as a last resort. 

The manufacturer sent letters last week to cancer doctors around the country to advise them of the latest findings.  

Company Vice President Ivan Horak said it should remain a standard therapy for advanced colorectal cancer. 

The drug works by blocking the ability of fast-multiplying cancer cells to copy their genetic material and divide. Doctors advise people 50 and older to get regular checkups for colorectal cancer.