New drug takes on intestinal cancer

For patients with a rare cancer called gastrointestinal stromal tumor, or GIST, there’s been no effective treatment other than surgery. That may change.

A new drug has helped more than three-quarters of GIST patients taking it. In these patients, surgery either failed or was impossible. The drug shrank or stopped tumor growth for at least 6 months from the beginning of treatment.

Between 5,000 and 10,000 people in the United States, and as many again worldwide, suffer from GIST, according to George Demetri of the Dana-Farber Cancer Institute in Boston.

GIST forms from cells similar to the ones that trigger the gut’s food-moving contractions. In these cells, a single mutation in a gene called C-KIT can lead to cancer. The mutation revs up an enzyme that attaches the amino acid tyrosine to proteins involved in signaling within cells. The resulting changes can cause gastrointestinal stromal cells to replicate uncontrollably.

The new drug, called imatinib mesylate, is made by Novartis Pharmaceutical Corp. in East Hanover, N.J., under the brand name Gleevec. The Food and Drug Administration earlier this month approved it for treating people with a form of leukemia. Because research in leukemia patients had shown that the drug blocks the activity of certain other enzymes that add tyrosine to proteins, Demetri and his international team reasoned that it also might work against C-KIT and GIST.

“Within the first month, some people lost as much as 20 pounds of tumor,” Demetri says. At this month’s meeting of the American Society of Clinical Oncology in San Francisco, his team presented data from a Novartis-funded trial showing that tumors in 51 of 86 patients shrank to less than half their original size within 7 months. Tumorss in another 22 people shrank less or stabilized. Tumor size increased in the remaining patients.

Side effects such as headaches and body swelling were generally mild. Seven of the 86 patients had serious internal bleeding, however. “The problem may be related to the success of the treatment,” Demetri says. “Suddenly, the blood vessels that used to feed these large tumors have nowhere to go.”

The National Cancer Institute has already begun a large international study to test imatinib mesylate against GIST.