Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial.
Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial.
复制标题
DOI：
10.1097/sla.0b013e3182a15eb7
复制
发表时间：
2013-09
影响因子：
9
通讯作者：
American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team for the Alliance for Clinical Trials in Oncology
中科院分区：
文献类型：
--
作者：
DeMatteo RP;Ballman KV;Antonescu CR;Corless C;Kolesnikova V;von Mehren M;McCarter MD;Norton J;Maki RG;Pisters PW;Demetri GD;Brennan MF;Owzar K;American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team for the Alliance for Clinical Trials in Oncology
开展甲磺酸伊马替尼治疗胃肠道间质瘤（GIST）的首个辅助试验。胃肠道间质瘤是最常见的肉瘤。虽然手术切除一直是局部原发性 GIST 的主要治疗方法，但术后肿瘤复发很常见。 KIT 原癌基因或较少见的血小板衍生生长因子受体 α (PDGFRA) 在 GIST 中发生突变；两者的基因产物均被甲磺酸伊马替尼抑制。这是一项由美国外科医师学会肿瘤学组 (ACOSOG) 领导的 II 期组间试验，在 ClinicalTrials.gov 上注册为 NCT00025246。从 09/2001 到 09/2003，我们收集了 106 名接受了肉眼肿瘤完全切除但被认为具有高复发风险的患者。患者接受伊马替尼 400 毫克/天治疗一年，随后进行系列放射学评估。主要终点是总生存期（OS）。中位随访 7.7 年后，1 年、3 年和 5 年 OS 率分别为 99%、97% 和 83%，与历史 5 年 OS 率 35% 相比毫不逊色。 1 年、3 年和 5 年 RFS 率为 96%、60% 和 40%。在单变量分析中，年龄和有丝分裂率与 OS 相关。多变量分析表明，RFS 率随着肿瘤大小、小肠部位、KIT 外显子 9 突变、高有丝分裂率和年龄的增加而降低。与历史对照相比，复发风险高的原发性 GIST 患者接受伊马替尼辅助治疗可延长 OS。辅助治疗的最佳持续时间仍未确定。 (NCT00025246)
To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST). GIST is the most common sarcoma. While surgical resection has been the mainstay of therapy for localized, primary GIST, postoperative tumor recurrence is common. The KIT proto-oncogene or, less frequently, platelet-derived growth factor receptor alpha (PDGFRA) is mutated in GIST; the gene products of both are inhibited by imatinib mesylate. This was a phase II, intergroup trial led by the American College of Surgeons Oncology Group (ACOSOG), registered at ClinicalTrials.gov as NCT00025246. From 09/2001 to 09/2003, we accrued 106 patients who had undergone complete gross tumor removal but were deemed at high risk for recurrence. Patients were prescribed imatinib 400 mg/day for 1 year and followed with serial radiologic evaluation. The primary endpoint was overall survival (OS). After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rate was 99, 97, and 83%, which compared favorably with a historical 5 year OS rate of 35%. The 1-, 3-, and 5-year RFS rate was 96, 60, and 40%. On univariable analysis, age and mitotic rate were associated with OS. On multivariable analysis, the RFS rate was lower with increasing tumor size, small bowel site, KIT exon 9 mutation, high mitotic rate, and older age. Adjuvant imatinib in patients with primary GIST who are at high risk of recurrence prolongs OS compared to that of historical controls. Optimal duration of adjuvant therapy remains undefined. (NCT00025246)