U.S. Food and Drug Administration, White Oak Campus, 10903 New Hampshire Avenue, Building 22, Room 2102, Silver Spring, Maryland 20993-0002, USA.
Oncologist. 2010;15(3):300-7. doi: 10.1634/theoncologist.2009-0120. Epub 2010 Mar 3.
On December 19, 2008, the U.S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec(R); Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal tumor (GIST). A randomized, double-blind, placebo-controlled study enrolling 713 patients was submitted. The primary objective of the clinical trial was to compare the recurrence-free survival (RFS) intervals of the two groups. Overall survival (OS) was a secondary endpoint. Eligible patients were > or =18 years of age with a histological diagnosis of GIST (Kit(+)), resected tumor size > or =3 cm, and a complete gross resection within 14-70 days prior to registration. Imatinib, 400 mg orally, was administered once daily for 1 year. The study was terminated after completion of the third protocol-specified interim analysis. At that time, 100 RFS events were confirmed by a blinded central independent review. With a median follow-up of 14 months, 30 RFS events were observed in the imatinib group and 70 were observed in the placebo group (hazard ratio, 0.398; 95% confidence interval, 0.259-0.610; two-sided p-value < .0001). OS results are immature. Most patients in both groups experienced at least one adverse reaction, and 31% of the imatinib group and 18% of the placebo group experienced grade > or =3 adverse reactions. The most frequently reported adverse reactions (> or =20%) were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Drug was discontinued for adverse reactions in 17% and 3% of the imatinib and placebo-treated patients, respectively.
2008 年 12 月 19 日，美国食品药品监督管理局批准甲磺酸伊马替尼片口服（格列卫®；诺华制药公司，东 Hanover，新泽西州）用于 Kit(+)（CD117(+)）胃肠道间质瘤（GIST）完全大体切除后的成人辅助治疗。提交了一项纳入 713 例患者的随机、双盲、安慰剂对照研究。临床试验的主要目的是比较两组患者的无复发生存期（RFS）。总生存期（OS）是次要终点。合格患者年龄 > 或 = 18 岁，组织学诊断为 GIST（Kit(+)），切除肿瘤大小 > 或 = 3cm，在登记前 14-70 天内进行完全大体切除。伊马替尼 400mg 口服，每日一次，持续 1 年。在完成第三次方案规定的中期分析后，研究终止。当时，通过盲法独立中心审查确认了 100 例 RFS 事件。中位随访 14 个月，伊马替尼组观察到 30 例 RFS 事件，安慰剂组观察到 70 例 RFS 事件（风险比，0.398；95%置信区间，0.259-0.610；双侧 p 值 <.0001）。OS 结果不成熟。两组患者大多数至少发生一次不良反应，伊马替尼组 31%和安慰剂组 18%的患者发生 > or =3 级不良反应。报告频率 > or = 20%的最常见不良反应为腹泻、疲劳、恶心、水肿、血红蛋白降低、皮疹、呕吐和腹痛。由于不良反应，分别有 17%和 3%的伊马替尼和安慰剂治疗患者停止用药。
