New drug might stop cancer by targeting genetic flaw that makes it grow

Daniel Q. Haney

Sunday, May 21, 2000 | 2:34 a.m.

NEW ORLEANS - A new drug that targets one of the basic genetic flaws in cancer shows promise in early tests on humans, halting the growth of tumors and making them more vulnerable to chemotherapy.

The medicine is one of many in development that attempt to shift cancer treatment away from a broad attack on all rapidly dividing cells. Instead, the new drugs focus on the precise genetic mutations that make tumors different from healthy tissue.

Many of these new drugs attempt to interfere with tumors' use of epidermal growth factor, one of the chemical signals that plays a crucial role in their survival.

On Sunday, researchers presented data on experimental use of one of these drugs, code-named IMC-C225. The drug was discovered by Dr. John Mendelsohn of Memorial Sloan-Kettering Cancer Center in New York City and is being developed by ImClone Systems Inc., which is financing the research.

Although studies are still in early stages, the drug shows potential in victims of colon cancer and head and neck cancer who have failed standard treatments.

By itself, the drug appears to make tumors stop growing. This, in turn, leaves them open to the killing power of standard chemotherapy drugs.

"It's a two-hit hypothesis," said Dr. Mark S. Rubin. "The one-two punch takes the cancer down."

Doctors say that almost every pharmaceutical company has drugs in testing that are intended to stop tumor growth by exploiting this and similar targets. The first drug in this category to reach the market was Genentech's Herceptin, which was approved in 1998.

Both Herceptin and IMC-C225 are antibodies that block epidermal growth factor receptors. These are spots on the cell that receive chemical signals prompting them to divide. Because of a genetic mutation, many cancer cells have extra copies of these receptors, which help fuel their out-of-control growth.

Herceptin blocks a growth factor receptor that is commonly found on breast cancer cells, while IMC-C225 is aimed at one found on a variety of other tumors.

Rubin, who is in private practice in Bonito Springs, Fla., was the first to test IMC-C225 against colon cancer. His first patient, treated a year ago, had failed to respond to standard chemotherapy, and her cancer had spread to her liver and abdomen.

On a combination of IMC-C225 and the chemotherapy drug Camptosar, the woman's spreading tumor shrank by 80 percent. The remnants of her cancer were then surgically removed, and she now appears well and free of all signs of the disease, although doctors cannot say how long the remission will last.

Doctors at several hospitals plan to test the drug in 125 colon cancer patients and in 98 with head and neck cancer. All have cancer that has failed all standard treatment.

Samuel D. Waksal, ImClone's president, said the treatment appears to have shrunk tumors by more than half in 12 patients with head and neck cancer and eight with colon cancer. This represents about 30 percent of the head and neck patients and 20 percent of those with colon cancer who have taken the drug long enough to make a difference.

The company also plans to sponsor experiments with the drug in victims of cancer of the pancreas, lung, ovaries and esophagus.

Dr. James Abbruzzese of the University of Texas M. D. Anderson Cancer Center in Houston is using the drug experimentally on patients with pancreatic cancer, which is especially difficult to treat. He said that while doctors are enthusiastic about the potential of this approach, he cautioned: "It's very preliminary. We don't want to overstate what we are seeing until we have an adequate amount of follow up time."

Nevertheless, Dr. Lori Goldstein of the Fox Chase Cancer Center in Philadelphia predicted that most cancer studies will soon involve similar treatments that go after the specific genetic disruptions that cause cancer to grow out of control.

"The hope is to characterize each tumor with DNA analysis to target the therapy directly," she said.