What's New In Sarcoma
Gleevec, formerly known as STI-571, is a novel signal transduction inhibitor that appears to be effective for the treatment of gastrointestinal stromal tumors (GIST), according to the results of phase I and phase II trials presented on Sunday at the annual meeting of the American Society of Clinical Oncology.
Previous laboratory investigations have shown that Gleevec inhibits the function of the proto-oncogene c-kit, which promotes cell proliferation in GIST, Dr. Charles D. Blanke from Oregon Health Sciences University in Portland told conference participants.
In a phase II trial, Dr. Blanke and colleagues administered Gleevec to 148 patients with metastatic or unresectable GIST in doses similar to those given to patients with chronic myeloid leukemia. The US Food and Drug Administration recently approved Gleevec for the treatment of chronic myeloid leukemia. (see Reuters Health report for May 5)
Patients were randomized to 400 mg or 600 mg daily oral doses of Gleevec and were evaluated with CT and PET scans and serial tumor tissue biopsy. At baseline, the investigators also confirmed the presence of the c-kit expression in the patients' tumors. A total of 139 patients were available for evaluation.
Fifty-nine percent of the patients had tumor shrinkage. "This is notable because there is no standard chemotherapy to help GIST patients," Dr. Blanke said. During an average follow-up of 4.5 months, no patients who remained on Gleevec and who had achieved a remission relapsed, he added.
Patients with kit mutations benefited more from the treatment than those without this mutation, with 86% of the patients with kit mutations having a remission rate of 78%, Dr. Blanke noted.
"This is the first effective nonsurgical therapy for GIST," he said. "The way we do cancer research will change; Gleevec is like a "guided missile, specifically targeting the defect that makes the GIST cell cancerous, while sparing most normal cells," he said.
In the second presentation, Dr. Allan
T. Van Oosterom from UZ Gasthuisberg KULeuven, Belgium, and
colleagues performed a phase I study with 36 GIST patients and 4
patients with other soft tissue sarcomas. The subjects received
Gleevec doses ranging from 400 mg twice daily to 500 mg twice daily.
After 8-to-12 weeks of therapy,
quality of life improved and most patients had resumed
working," Dr. Van Oosterom added. Thirteen patients had a
confirmed partial response and 12 patients had an unconfirmed
"Since 33 of 36 of our patients are still on the treatment, I believe that with Gleevec we have changed the natural course of this disease," Dr. Van Oosterom concluded.
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