Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial
Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial
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DOI：
10.1016/s0140-6736(04)17098-0
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发表时间：
2004-09-25
期刊：
影响因子：
168.9
通讯作者：
Judson, I
中科院分区：
文献类型：
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作者：
Verweij, J;Casali, PG;Judson, I
背景伊马替尼在全球范围内被批准用于胃肠道间质瘤（GIST）。我们的目的是评估使用伊马替尼治疗转移性GIST的疗效和无进展生存期的剂量依赖性。方法946例患者随机给予伊马替尼400mg，每日1次或2次。那些每天一次的治疗方案有进展的患者可以选择交叉治疗。主要终点为无进展生存期。分析的目的是治疗。在中位随访760天（IQR 644-859）时，分配每天一次伊马替尼的473例患者中有263例（56%）进展，而分配每天两次治疗的473例患者中有235例（50%）进展（估计风险比0-82 [95% Cl 0-69-0-98]； p = 0.026）。465/470（99%）患者每天接受一次治疗，而468/472（99%）患者每天接受两次治疗。与每天治疗一次的组相比，每天治疗两次的患者有更多的剂量减少（77例[16%]对282例[60%]）和治疗中断（189例[40%]对302例[64%]），但两组的治疗耐受性都相当好。52例（5%）患者完全缓解，442例（47%）患者部分缓解，300例（32%）患者病情稳定，组间无差异。达到最佳反应的中位时间为107天（IQR 58-172）。如果反应诱导是治疗的唯一目的，日剂量400mg伊马替尼是足够的；然而，每天两次400毫克的剂量可以显著延长无进展生存期。
Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST.Methods 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat.Findings At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0-82 [95% Cl 0-69-0-98]; p = 0.026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172).Interpretation If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.