"These impressive positive results in gastrointestinal stromal tumors, a form of sarcoma which is highly resistant to any conventional chemotherapy, are very exciting news for these patients, who had essentially no effective treatment options before Gleevec [imatinib]," said George D. Demetri, MD, lead author. "These data support the observations that the anticancer responses with Gleevec [in gastrointestinal stromal tumor] patients are often durable. It is clear that this treatment can shrink even massive tumors in the majority of patients with this malignancy, by targeting and inhibiting the mutant enzyme which is abnormally active in this tumor type."

The current study was a Phase II, open-label, randomized, international, multicenter trial that evaluated treatment in 147 patients, who were randomized to either 400 mg (N=73) or 600 mg (N=74) of imatinib once daily. All patients had advanced disease and most had previously failed other treatments, including surgery, chemotherapy, and radiation therapy.

The authors reported that tumor responses remained durable for more than 46 weeks and that a median duration of response had not yet been reached at the point data were analyzed for the article. The estimated one-year survival rate is 88 percent, but the median survival rate has not yet been established.

Imatinib was originally submitted for approval in the U.S. for use with KIT-positive unresectable or metastatic gastrointestinal stromal tumors--- that is, advanced tumors positive for activation of the KIT receptor tyrosine kinase enzyme. Imatinib is a selective tyrosine kinase inhibitor that has shown antitumor activity in preclinical models and in preliminary clinical studies.

Although the majority of patients had adverse events reported at least once during the trial, most events were mild to moderate in severity and included nausea, diarrhea, periorbital edema, muscle cramps, fatigue, headache and skin rash. Serious (Grades 3-4) adverse events occurred in 21.1 percent of patients overall. They included low white blood cell counts, tumor hemorrhage, and abdominal pain. There was no significant difference in adverse effects or tumor response between the two dosage levels.

Based on a 54-percent partial response rate and a 28-percent rate for stable disease, as well as the sustained duration of response, the authors conclude that use of imatinib as an enzyme inhibitor shows promise against a tumor type that has proved resistant to conventional therapies.