Test Shows Who'll Respond to Gleevec

Finds gene mutation causing gastrointestinal cancer

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By
HealthDay Reporter

WEDNESDAY, Dec. 3, 2003 (HealthDayNews) -- A simple lab test can reveal how well patients with a particularly deadly gastrointestinal cancer will respond to the cancer-fighting drug Gleevec, a new study finds.

The test is designed to determine the particular type of gene mutation causing the cancer. Patients with a favorable test result had an 84 percent chance of partial remission after taking Gleevec, researchers report in the current issue of the Journal of Clinical Oncology. None of those with unfavorable test results experienced partial remission.

"It allows us to predict ahead of time the likelihood of responding to Gleevec," says study coauthor Dr. Michael Heinrich, an associate professor of medicine at Oregon Health & Science University School of Medicine in Portland.

As many as 10,000 Americans each year are diagnosed with so-called gastrointestinal stromal tumors (GISTs), a kind of soft-tissue sarcoma occurring along the digestive tract. While surgery is the conventional treatment, it may not be effective in patients whose tumors recur or spread to other parts of the body.

Before Gleevec, an oral cancer drug marketed by Novartis Pharmaceuticals Corp., patients with GIST lived an average of 20 months.

The medication was first approved in May 2001 for treating chronic myeloid leukemia, a type of cancer affecting the body's white blood cells. Less than a year later, the U.S. Food and Drug Administration cleared it for use in treating patients with GIST.

Gleevec is known as a tyrosine kinase inhibitor. It works by shutting down enzymes in the body that cause cells to become cancerous. It does that by inhibiting growth of a protein called KIT that spurs growth of the cancerous cells.

In clinical testing, the anticancer drug showed tremendous promise. A majority of patients with advanced GIST who were treated with Gleevec responded well. For them, the drug opened the possibility of long-term survival.

Some, though, did not respond positively. The latest study was designed to understand why.

Researchers analyzed DNA samples of GIST tumors from 127 patients who were enrolled in Phase II testing of the drug. The results revealed three distinct groups of patients. Those with a specific type of KIT mutation called "exon 11" fared best, with an 84 percent chance that their tumors would shrink by at least 50 percent. They also lived longer than patients with a different type of KIT mutation or no mutation at all.

Patients with a KIT mutation called "exon 9" had a 48 percent chance of reducing their tumors by half or more. But they did not live as long, with half failing treatment after 187 days.

GIST patients that lacked a KIT mutation did not respond well to the drug at all.

The findings point to the value of testing for specific mutation type. "It allows you and your physician to have a better prognosis," Heinrich explains. "I envision the day, not just for GIST, that when you're diagnosed, your treatment will be individualized."

Dr. George D. Demetri, director of the Dana-Farber Cancer Institute's Center for Sarcoma and Bone Oncology in Boston, agrees. Focusing on genetic mutations and how different drugs respond will give researchers "a much better understanding of what makes the cancer tick and to designing drugs that will battle it," he says.

Still, the latest findings should not discourage doctors from at least giving the drug a try, he cautions.

"We can't predict for certain who will and will not respond. And since this is the best drug around for the treatment of metastatic GIST, I would hate for any doctor or patient to operate under the misconception that they shouldn't try Gleevec," Demetri urges.

More information

Learn about gastrointestinal tumors from the American Cancer Society, while MedlinePlus has a primer on Gleevec.

SOURCES: Michael Heinrich, M.D., associate professor, medicine, Oregon Health & Science University School of Medicine and Portland VA Medical Center; George D. Demetri, M.D., director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and associate professor, medicine, Harvard Medical School, Boston; Dec. 1, 2003, Journal of Clinical Oncology

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