Monday, April 16, 2007

ACOSOG study finds use of Gleevec reduces cancer recurrence for patients with primary gastrointestinal stromal tumor (GIST)
by Julie McKeel

Early results from a clinical trial for patients with primary gastrointestinal stromal tumor (GIST) 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.

[GIST is a type of cancer that develops in the cells of the body's connective or supportive tissues. The tumors for GIST patients are usually found in the stomach or small intestine. It is estimated that approximately 5,000 to 6,000 new patients are diagnosed with GIST each year in the United States.]

This large, randomized, placebo-controlled 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).

A recent interim analysis showed that the study had met its primary endpoint of increasing recurrence-free survival, thus the data monitoring committee overseeing the ACOSOG Z9001* trial recommended that the results from the analysis be made public. Detailed results from this trial will be presented at a future scientific meeting.

The findings reveal that approximately 97% of the study patients who received one year of imatinib after surgery did not have a recurrence of their cancer compared to 83% of patients who were given the placebo. The imatinib therapy was well tolerated by most patients enrolled in the study. Side effects were typical for imatinib, including nausea, diarrhea, and swelling.

According to the research team, the results have major implications for patients with primary GIST. While conventional chemotherapy agents have been ineffective in treating GIST, this study demonstrated that targeted molecular therapy reduces the rate of recurrence after complete removal of a primary GIST.

"The standard treatment for primary GIST is complete surgical removal of the tumor without additional therapy," NIH Director Elias A. Zerhouni, M.D. told the NCI news office. "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."

Over 600 patients participated in the trial between June 2002 and April 2007 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. These patients were randomized to either the imatinib group or the placebo group. The imatinib patient group received a 400 milligrams dose per day for one year, while the second group received placebo for one year.

Patients who developed a recurrence of their cancer while participating in the study were unblinded to their treatment assignment. The placebo patients subsequently received imatinib and while those who had been on imatinib continued their imatinib therapy, but at a higher dose. There was no difference in overall survival for patients in either group.

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.

* [Z9001: A Phase III Randomized Double-blind Study of Adjuvant STI571 (Gleevec®) Versus Placebo in Patients Following the Resection of Primary Gastrointestinal Stromal Tumor (GIST)]