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Imatinib Mesylate Promising in Advanced Gastrointestinal Stromal Tumours
New England Journal of Medicine (NEJM)
08/15/2002
By Anne MacLennan
Inhibition of the KIT signal-transduction pathway is showing promise in the treatment of advanced gastrointestinal (GI) tumours
Researchers from Dana-Farber Cancer Institute and Harvard Cancer Center, Boston, Massachusetts, and other centres in the United States, Finland and Switzerland, report that none of the 147 patients in their study had a complete response, 79 (53.7 percent) had a partial response and 41 (27.9 percent) had stable disease.
For technical reasons, response could not be evaluated in seven patients (4.8 percent).
Preclinical models and preliminary clinical studies have shown imatinib mesylate - a selective tyrosine kinase inhibitor-to have activity against GI stromal tumours.
Median duration of survival for patients with a metastatic GI stromal tumour is approximately 20 months, and nine to 12 months for patients with local recurrence. Most GI stromal tumours have a defect in KIT, a transmembrane tyrosine kinase receptor, which prevents the death of the cell and forces it to proliferate.
None of the total of 147 patients had a complete response, 79 (53.7 percent) had a partial response and 41 (27.9 percent) had stable disease. For technical reasons, response could not be evaluated in seven patients (4.8 percent).
Median duration of response had not been reached after a median follow-up of 24 weeks. Twenty of the patients (13.6 percent) showed early resistance to treatment.
The therapy was well tolerated, although mild-to-moderate oedema, diarrhea and fatigue were common, and gastrointestinal or intra-abdominal haemorrhage occurred in approximately five percent of patients. There were no significant differences in toxic effects or response between the two doses.
Longer follow-up will be needed to determine whether the drug actually prolongs life.
N Engl J Med 2002;347:472-480.
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