Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients
Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients
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DOI：
10.1007/s10147-011-0339-7
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发表时间：
2013-02-01
影响因子：
3.3
通讯作者：
Ohtsu, Atsushi
中科院分区：
文献类型：
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作者：
Kanda, Tatsuo;Nishida, Toshirou;Ohtsu, Atsushi
甲磺酸伊马替尼是一种小分子酪氨酸激酶抑制剂，目前用于高危胃肠道间质瘤(GIST)切除患者的辅助治疗。目前尚无关于日本或东亚GIST患者术后应用伊马替尼的有效性和安全性的数据。在日本的17家医院进行了一项单臂、开放标签、多中心的试验。资格标准包括组织学证实的原发高危GIST，并进行了大体完全切除。术后给予伊马替尼400 mg/d，连用1年。Kaplan-Meier分析评估的主要终点是无复发生存期。次要终点是总体存活率和安全性。本研究在临床试验网站上注册，编号NCT00171977。研究对象为2004年9月至2006年7月间的患者。患者的中位年龄为59.5岁。49名患者(76.6%)完成了为期一年的治疗，而15名患者(23.4%)由于复发、毒性和撤回同意而没有完成治疗。在109周的中位随访期内，有20名患者复发。3年复发率为42.7%(95%可信区间29.2~56.3%)，超过本试验的预期复发率。2年无复发生存率为71.1%，总生存率为93.7%。所有级别中最常见的不良反应是眼皮水肿(48.4%)，其次是中性粒细胞减少(40.6%)、白细胞减少(39.1%)、恶心(39.1%)、皮疹(37.5%)和周围水肿(37.5%)，大多数都是轻微和可控的。日本患者对伊马替尼400 mg/天的辅助治疗1年耐受性良好，可能会降低高危GIST早期复发的风险。
Imatinib mesylate, a small-molecule tyrosine kinase inhibitor, is currently used for adjuvant therapy of patients who have undergone resection of high-risk gastrointestinal stromal tumors (GISTs). There are no data concerning the efficacy and safety of postoperative adjuvant therapy with imatinib for Japanese or East Asian patients with GIST.A single-arm, open-label, multicenter trial was conducted in 17 hospitals in Japan. The eligibility criteria included histologically proven primary high-risk GISTs with macroscopic complete resection. Patients were treated with imatinib at a dose of 400 mg/day for 1 year after surgery. The primary endpoint was recurrence-free survival as assessed by Kaplan-Meier analysis. The secondary endpoints were overall survival and safety. This study was registered with ClinicalTrials.gov, number NCT00171977.A total of 64 patients were enrolled between September 2004 and July 2006. The median age of the patients was 59.5 years. Forty-nine (76.6%) patients completed the 1-year treatment, whereas 15 (23.4%) patients did not complete the treatment owing to recurrence, toxicities, and consent withdrawal. At the median follow-up period of 109 weeks, 20 patients had recurrence. The 3-year recurrence rate was 42.7% (95% confidence interval 29.2-56.3%), which exceeded the expected recurrence rate in this trial. The recurrence-free and overall survival rates at 2 years were 71.1 and 93.7%, respectively. The most frequent adverse drug reaction of any grade was eyelid edema (48.4%), followed by neutropenia (40.6%), leukopenia (39.1%), nausea (39.1%), rash (37.5%), and peripheral edema (37.5%), most of which were mild and manageable.Adjuvant therapy with imatinib at 400 mg/day for 1 year is well tolerated by Japanese patients and possibly reduces the risk of early recurrence of high-risk GISTs.