胃肠道间质瘤(GIST)诊断和治疗进展技术方案.ppt

Imatinib Mesylate in GIST: Clinical Efficacy First Patient With GIST to Receive Imatinib Mesylate: Proof-of-Concept Exploratory study with a single patient with oral imatinib mesylate at 400 mg/d Dramatic clinical response Disappearance of excess metabolic activity at 4 weeks by 18FDG-PET 75% reduction in tumor size at 8-month follow-up Tumor biopsies showed histologic evidence of myxoid degeneration and lack of mitotic activity Symptomatic relief EORTC Phase I Study of Imatinib Mesylate in GIST and Other Sarcomas: Study Design 90% of patients had confirmed KIT-positive GIST 75% of patients had metastases in the liver 60% of patients had received prior chemotherapy EORTC Phase I Trial: Conclusions At a range of doses from 400-1000 mg/d, 800 mg/d is the MTD Imatinib mesylate has significant activity in patients with advanced GIST (n=35), but little or no activity in non-GIST patients Imatinib Mesylate in GIST: Pivotal Phase II Trial Study Design Imatinib Mesylate in GIST: Pivotal Trial—Study Design (cont’d) Imatinib Mesylate in GIST:Evolution of Tumor Responses Over Time Imatinib Mesylate in GIST: Pivotal Trial—Overall Survival With a median follow-up of 34 months, median survival has not been reached Imatinib Mesylate in GIST: Pivotal Trial—Conclusions 147 patients randomized to 400 or 600 mg/d 83% of patients showed a clinical benefit 67% PR/CR 16% stable disease (SD) Median time to progression (TTP) was 84 weeks Median overall survival (OS) has not been reached at median follow-up of 34 months Imatinib mesylate has an acceptable safety profile in patients with GIST Imatinib Mesylate Indication Indicated dose for patients with KIT-positive, unresectable or metastatic malignant GIST is 400 or 600 mg/d 400 mg/d effects a mean plasma concentration of imatinib mesylate of1.46 μM Imatinib mesylate should be taken with food and a large glass of water to minimize GI irritation Imatinib Mesylate in GIST: EORTC Phase II Trial Trial included patients with GIST or