|Gleevec Decreases Cancer Recurrence for Patients
with Primary Gastrointestinal Stromal Tumor
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).
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