Preliminary results from a large, randomized, placebo-controlled clinical trial for patients with primary gastrointestinal stromal tumor (GIST), a type of tumor usually found in the stomach or small intestine, showed that patients who received imatinib mesylate (Gleevec®) after complete removal of their tumor were significantly less likely to have a recurrence of their cancer compared to those who did not receive imatinib. The clinical trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and conducted by a network of researchers led by the American College of Surgeons Oncology Group (ACOSOG).

The data monitoring committee overseeing the trial (known as ACOSOG Z9001) recommended that the results from a recent interim analysis be made public because the study had met is primary endpoint of increasing recurrence-free survival.

“The standard treatment for primary GIST is complete surgical removal of the tumor without additional therapy,” said Elias A. Zerhouni, M.D., NIH Director. “It is excellent news that addition of this well-tolerated cancer pill to the treatment regimen can have such a positive impact on decreasing the risk of recurrence.”

Researchers found that approximately 97 per cent of patients in the study who received one year of imatinib after surgery did not have a recurrence of their cancer compared to 83 percent of patients who received one year of placebo. In addition, imatinib therapy was well tolerated by most patients enrolled in the study. The types of side effects observed in this trial were similar to those observed in other clinical trials with imatinib, and included nausea, diarrhea, and swelling. Presentation of detailed results from this trial is planned for a future scientific meeting.

“These results have major implications for patients with primary GIST,” noted the principal investigator of the study, Ronald DeMatteo, M.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y. “Conventional chemotherapy agents have been notoriously ineffective in GIST. This study for the first time demonstrated that targeted molecular therapy reduces the rate of recurrence after complete removal of a primary GIST.” Information on over 600 patients enrolled on this study was used in the analysis. Patients participated through one of five NCI-sponsored North American Cooperative Oncology Groups, led by ACOSOG and including Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Southwest Oncology Group, and the National Cancer Institute of Canada, Clinical Trials Group.

Patients with primary tumors three centimeters or larger that had been completely removed with surgery were enrolled in the trial between June 2002 and April 2007. Patients were randomized to one of two treatment arms. One patient group received imatinib at a dose of 400 milligrams per day for one year. The second group received placebo for one year. Neither the patients nor their physicians knew which treatment the patients were receiving. Patients who developed a recurrence of their cancer while on study therapy were unblinded to their treatment assignment. Those patients who had been on placebo subsequently received imatinib and those who had been on imatinib continued their imatinib therapy, but at a higher dose. There was no difference in overall survival for patients on the two treatment arms.

“Gleevec was one of the first targeted therapies that showed remarkable efficacy in clinical trials,” said NCI Director John E. Niederhuber, M.D. “These current results emphasize the need to continue to investigate all possible uses of these cutting edge drugs and to make them available to as many patients as possible.”

Gleevec, which belongs to a class of agents that block cellular communication to prevent tumor growth, was approved by the U.S. Food and Drug Administration in 2002 for the treatment of unresectable or metastatic GIST. Novartis Pharmaceutical Corporation, East Hanover, N.J., provided Gleevec for this trial and partial funding under a Cooperative Research and Development Agreement (CRADA) with NCI for the clinical development of imatinib. Partial support for the trial was also provided by the American College of Surgeons.

Gastrointestinal stromal tumor (GIST) is a sarcoma, which is a type of cancer that develops in the cells of the body’s connective or supportive tissues. GIST arises within the gastrointestinal tract. It is estimated that approximately 5,000 to 6,000 new patients are diagnosed with GIST each year in the United States.

The protocol for this study can be found at http://www.cancer.gov/clinicaltrials/ACOSOG-Z9001.

For more information about cancer, please visit the NCI website at http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.