Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: The French Sarcoma Group
Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: The French Sarcoma Group
复制标题
DOI：
10.1200/jco.2006.09.0183
复制
发表时间：
2007-03-20
影响因子：
45.3
通讯作者：
Perol, David
中科院分区：
文献类型：
--
作者：
Blay, Jean-Yves;Le Cesne, Axel;Perol, David
目的伊马替尼是晚期胃肠道间质瘤（GIST）的标准治疗药物。目前尚不清楚伊马替尼是否可以停止在患者中的疾病control.Methods前瞻性，随机，多中心III期研究的目的是比较连续（CONT）与中断（INT）伊马替尼超过1年的治疗晚期胃肠道间质瘤患者。主要终点是无进展生存期。次要终点包括总生存率、重新开始伊马替尼治疗后的缓解率和生活质量。早期停止规则的情况下，疾病的快速进展进行了定义，与预先计划的中期analysis.Results 2002年5月至2004年4月，182例晚期GIST患者入组。2003年5月至2004年4月，98例伊马替尼治疗后缓解或病情稳定的患者随访超过1年。40例患者不符合随机化条件，58例患者被随机分配，INT组和CONT组分别有32例和26例患者。截至2005年10月15日，CONT组26例患者中有8例和INT组32例患者中有26例记录到疾病进展（P <0.0001）。INT组26例记录到进展的患者中有24例对伊马替尼重新治疗有应答。两组之间未观察到总生存率或伊马替尼耐药的差异。生活质量评价6个月后，随机分配使用30项生活质量问卷两组之间的随机分配patients.Conclusion伊马替尼中断结果在大多数晚期GIST患者的快速进展，并不能推荐在常规的做法，除非患者经历显着的毒性。
Purpose Imatinib is the standard treatment of advanced GI stromal tumors (GISTs). It is not known whether imatinib may be stopped in patients in whom disease is controlled.Methods This prospective, randomized, multicentric phase III study was designed to compare continuous (CONT) compared with interrupted (INT) imatinib beyond 1 year of treatment in patients with advanced GIST. The primary end point was progression-free survival. Secondary end points included overall survival, response rate after reinitiation of imatinib, and quality of life. Early stopping rules in cases of rapid progression of disease were defined, with preplanned interim analyses.Results Between May 2002 and April 2004, 182 patients with advanced GIST were enrolled. Between May 2003 and April 2004, 98 patients in response or stable disease under imatinib reached more than 1 year of follow-up. Forty were not eligible for randomization, and 58 patients were randomly assigned, 32 and 26 patients in the INT and CONT arms, respectively. As of October 15, 2005, eight of 26 patients in the CONT group and 26 of 32 patients in the INT group had documented disease progression (P < .0001). Twenty-four of 26 patients with documented progression in the INT arm responded to imatinib reintroduction. No differences in overall survival or imatinib resistance were observed between the two arms. Quality of life evaluated 6 months after random assignment using the 30-item Quality of Life Questionnaire was not significantly different between the two groups of randomly assigned patients.Conclusion Imatinib interruption results in rapid progression in most patients with advanced GIST, and cannot be recommended in routine practice unless patient experience significant toxicity.