Initial and Late Resistance to Imatinib in Advanced Gastrointestinal Stromal Tumors Are Predicted by Different Prognostic Factors: A European Organisation for Research and Treatment of Cancer–Italian Sarcoma Group–Australasian Gastrointestinal Trials Group Study

作者：Martine Van Glabbeke, Jaap Verweij, Paolo Giovanni Casali, Axel Le Cesne, Peter Hohenberger, Isabelle L. Ray-Coquard, Marcus Schlemmer, Allan T. van Oosterom, David B Goldstein, Raf Sciot, Pancras C.W. Hogendoorn, Michelle Brown, Rossella Bertulli, Ian Robert Judson · 发表于：Journal of Clinical Oncology · 年份：2005 · DOI：10.1200/jco.2005.11.601 · 被引用次数：280 · 研究领域：Gastrointestinal Tumor Research and Treatment、Gastric Cancer Management and Outcomes、Gastrointestinal disorders and treatments

PURPOSE: The aim of this study was to identify factors predicting initial and late resistance of GI stromal tumor (GIST) patients to imatinib and to document the dose-response relationship in the prognostic subgroups. This study is based on the European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group randomized trial comparing two doses of imatinib in advanced disease. PATIENTS AND METHODS: Initial resistance was defined as progression within 3 months of randomization, and late resistance was defined as progression beyond 3 months. Investigated cofactors include imatinib dose, age, sex, performance status, original disease site, site and size of lesions at trial entry, and baseline hematologic and biologic parameters. RESULTS: Initial resistance was recorded for 116 (12%) of 934 assessable patients and was independently predicted by the presence of lung and absence of liver metastases, low hemoglobin level, and high granulocyte count. Among 818 patients who were alive and progression free at 3 months, 347 subsequent progressions were recorded, and late resistance was independently predicted by high baseline granulocyte count, primary tumor outside of the stomach, large tumor size, and low initial imatinib dose. The impact of initial dose on late resistance was mainly significant in patients with a high baseline granulocyte count (> 5.10(9)/L) and in patients with tumors of GI origin outside of the stomach and ...