Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal Tumors

Unresectable or metastatic gastrointestinal stromal tumors fail to respond to conventional chemotherapy and are usually fatal within 12 to 18 months. Most gastrointestinal stromal tumors have a defect in KIT, a transmembrane tyrosine kinase receptor. The abnormality prevents the death of the cell and forces it to proliferate. The effects of imatinib mesylate, which blocks the abnormal signaling by KIT, was studied in 147 patients with advanced gastrointestinal stromal tumors. There were no complete responses, but about half the patients had a stable partial response. Of 147 patients with advanced stromal tumors, about half had a stable partial response to imatinib mesylate. Gastrointestinal stromal tumors are mesenchymal neoplasms that appear to be related to the interstitial cells of Cajal of the myenteric plexus, with which they share certain differentiation markers. 1 , 2 Gastrointestinal stromal tumors express the cell-surface transmembrane receptor KIT that has tyrosine kinase activity and is the protein product of the KIT proto-oncogene. There are frequent gain-of-function mutations of KIT in gastrointestinal stromal tumors. 3 , 4 These mutations result in the constitutive activation of KIT signaling, which leads to uncontrolled cell proliferation and resistance to apoptosis. It has recently been reported that KIT activation occurs in all cases of gastrointestinal stromal tumor, . . .