New cancer drug may shrink large tumors

by MIKE MARTIN, UPI Science Correspondent

NEW YORK, May 12 (UPI) -- Studies of IMC-C225, a new drug for the treatment of advanced-stage colorectal cancer, show it can shrink tumors in some patients who have developed resistance to other chemotherapy agents.

Clinical trial director Dr. Leonard Saltz, of New York City's Memorial Sloan-Kettering Cancer Center, reports his findings today at the American Society of Clinical Oncology's Annual Meeting in San Francisco.

IMC-C225, or cetuximab, takes its name from drug company ImClone Systems, a small manufacturer located in New York City. ImClone makes cetuximab and a number of other potential cancer therapies.

In trials, Dr. Saltz and his team gave IMC-C225 to 120 patients with widespread colorectal cancer whose tumors no longer responded to standard chemotherapy. Saltz reports 22.5 percent of them had their tumors shrink 50 percent or more when the new drug was used in combination with standard chemotherapeutic agents. An additional 7.5 percent achieved stable disease.

"This is a significant result," said Dr. Saltz. "We have a group of patients who have failed to respond to two other therapies, and now we're getting a 22.5 percent response rate from this new regimen."

Colorectal cancer, Saltz noted, is the second leading cause of cancer death, with an estimated 56,300 men and women expected to die this year in the United States alone.
"IMC-C225 binds to the epidermal growth factor receptor on colorectal tumors," said

Dr. David Kelsen, chief of gastrointestinal oncology for Memorial Sloan-Kettering and not involved with the study group. "IMC-C225 follows the strategy not to kill tumor cells, but rather it binds to docking ports on the surface of certain cells. There, it interferes with a variety of chemical signals sent down cellular pathways to other cells. The net effect is that more tumor cells die than are produced, shrinking the tumor."

According to Saltz, IMC-C225 is a monoclonal antibody that works well on colorectal tumors because some 72% of these tumors test positive for epidermal growth factor.

Dr. Kelsen told United Press International the new drug has few side effects other than a rash. "But since it is so often use in combination with other chemotherapy agents, it's hard to tell precisely what side effects it may have," Kelsen explained.

According to Dr. Saltz, IMC-C225 is a good example of the next wave in cancer-drug development: targeted therapies based on an intricate understanding of the cancer cell.
As such, it has been the target of much interest and recent controversy.

Last Sunday the television news program 60 Minutes reported the stories of two women suffering from end-stage colorectal cancer. Both women sought IMC-C225 treatment through the FDA's so-called "expanded" or "compassionate access" program. One woman received the drug from ImClone, presumably because of a chance telephone conversation with ImClone president Samuel Waksal; the second did not and later passed away.

"You grapple with issues like this every day as a small company," said Andrea Rabney,
ImClone corporate communications vice president. "I'm thankful our president came out looking well in the report, because with all the varied issues involved in compassionate access, it's too easy to paint a company as a devil when the company is really just trying to deal with a very complicated situation."

David Kelsen concurred. He explained that expanded access is desirable only in select cases, and denial of such access should not be misinterpreted. "Only at different points in the stages of drug approval can expanded access be provided," Kelsen said. "Early in the process, not all of the toxicities are well understood, and the potential benefit to a particular patient may be in doubt. Later, when many of these issues have been worked out, expanded access can allow promising agents not yet fully approved to be used with patients who may benefit."

IMC-C225 may prove useful in expanded access at some point, Kelsen explained. Promising drugs such as IMC-C225 tend to attract greater than average attention, sometimes too soon.

"There's a lot of interest in this drug, administered both alone and in combination with other therapies," Kelsen said.

IMC-C225 may be ready for public use as early as 2002 Andrea Rabney told UPI.
It is also being used to treat head, neck, lung, and pancreatic cancers she said.