ROCKVILLE, Maryland—The Food and Drug Administration (FDA) has approved the use of Gleevec (imatinib mesylate, Novartis) for the treatment of c-kit-positive inoperable and metastatic malignant gastrointestinal stromal tumors (GISTs).
The FDA granted marketing approval on the basis of objective response to Gleevec that was established in a phase II study of 147 GIST patients, 38% of whom showed a partial response to treatment with the oral medication. Gleevec was originally approved on May 10, 2001, for the treatment of three stages of chronic myeloid leukemia (CML)—myeloid blast crisis, accelerated, and chronic.
"This is the first time we have seen such encouraging results in a drug used to combat GISTs," said George Demetri, MD, of the Dana-Farber Cancer Institute, who led the open-label, international study. "Gleevec represents the most major advance to date for a patient population that has had no alternative other than surgery for treating this resistant disease."
GISTs are the most common form of gastrointestinal tract sarcoma and affect an estimated 2,000 to 5,000 people in the United States. Patients with unresectable or metastatic GISTs have been considered incurable and essentially untreat-able, with a median survival of about 10 to 12 months.
In the study reviewed by the FDA, researchers randomized 147 patients to receive either 400 mg or 600 mg of Gleevec daily for up to 24 months. Although none of the participants had a complete response to the oral medication, 56 patients—33% of the 400-mg arm and 43% of the 600-mg group—had a partial response, defined as a reduction in tumor size of 50% or more. None of the patients in the study had been followed long enough to determine a meaningful response duration.
Most patients experienced an adverse side effect at least once while taking Gleevec, but most of the events were mild or modest in severity.
The most common events were edema, nausea, vomiting, diarrhea, abdominal pain, liver toxicity, neutropenia, thrombocytopenia, muscle cramps, skin rash, and fatigue.
