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Imatinib Gives Sustained Response in Gastrointestinal Stromal Cancer: Presented at ASCO-GI

By Roberta Friedman, PhD

SAN FRANCISCO, CA -- January 23, 2004 -- Advanced gastrointestinal stromal cancer (GIST) can be contained on a long term basis with continued imatinib therapy, according to results presented here at the First Annual Symposium on Gastrointestinal Cancers, sponsored jointly by the American Society of Clinical Oncology and other societies (ASCO-GI).

In Phase II findings reported previously, inoperable GIST responded well to the imatinib. During his presentation at ASCO-GI here January 22^nd, Charles Blanke, MD, Oregon Health Sciences University Cancer Institute, Portland, Oregon, said the benefit of imatinib treatment has lasted through a median follow up of 21 months. The drug, Dr. Blanke said, "remains the most effective therapy" for GIST.

The 95% partial response rate obtained with imatinib is superior to findings with other agents, Dr. Blanke said. In particular, those patients with a mutation in exon 11 KIT showed median event free survival of more than 24 months. Median time to treatment response was 3.3 months.

None of the patients who lacked either a KIT mutation or the platelet derived growth factor receptor (PDGFRA) in their tumor had a response to the agent.

In Dr. Blanke's trial, patients with advanced GIST who were not candidates for surgical treatment received either 400 mg or 600 mg daily of imatinib. Median survival has not yet been met in follow up, which has ranged from 21 to 43 months. Two thirds of patients still have not failed treatment at 15 months.

Dr. Blanke said that treatment continues indefinitely unless toxicity develops. Forty-six percent of the patients are still on active therapy. Adverse effects include diarrhea, nausea, and changes in liver enzymes. A quarter of patients had grade 3 or 4 toxicities, but these were not more common in the higher dose arm of the trial.

In response to questions from the audience, Dr. Blanke said that resistance appears to involve new mutations, "which we hope to use to identify new targets" for better therapeutics. "Surgery used to be the only thing that worked at all [for GIST]," Dr. Blanke said, "and that salvaged only 5% [of patients]."

For those patients that do progress, Dr. Blanke said, "don't stop the imatinib. Increase the dose if it was low -- 30% will still achieve stable disease." And if the disease is at a solitary site, remove it surgically, he added. Try other investigational drugs as well, Dr. Blanke recommended.


[Study title: Long-term follow up of advanced gastrointestinal stromal tumor (GIST) patients treated with imatinib mesylate. Abstract OP2]

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