FDA approves new drug for gastrointestinal stromal tumors.

On February 1, the U.S. Food and Drug Administration (FDA) approved GleevecTM (imantinib mesylate, Novartis Pharmaceuticals, Basel, Switzerland) for the treatment of patients with metastatic or unresectable malignant gastrointestinal stromal tumors (GIST). Gleevec was assessed in a single, open-label randomized trial at one center in Finland and three centers in the United States. A total of 147 patients were enrolled, with 73 randomized to receive 400 mg of Gleevec daily and 74 randomized to receive 600 mg daily. At the cutoff date for the study report, an overall objective response was confirmed in 56 patients, for an overall response rate of 38% (95% confidence interval 30%, 46%). These were all partial responses, and no complete responses were observed. The study was not powered to show a statistically significant difference in response rate between the two dose groups. Most adverse side effects were of mild to moderate severity and included interstitial edema, fluid retention (i.e., ascites, pleural effusion), nausea, vomiting, diarrhea, myalgias, skin rash, bone marrow suppression, bleeding, and elevations in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, or bilirubin. Hemorrhagic events included bleeding into the gastrointestinal tract or tumor sites, which occurred in seven patients (5%) and was not correlated with thrombocytopenia or tumor bulk. Adverse events were similar in patients receiving Gleevec 400 or 600 mg daily, in males and females, and in patients older or younger than age 65. The approved dose for the treatment of patients with GIST is 400 or 600 mg daily. For full prescribing information, including clinical trial information, safety, dosing, drug interactions, and contraindications, visit www.fda.gov/cder.foi/label/2002/ 21335s1lbl.pdf.