Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure
Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure
复制标题
DOI：
10.1016/j.ejca.2009.02.011
复制
发表时间：
2009-07-01
影响因子：
8.4
通讯作者：
Demetri, G. D.
中科院分区：
文献类型：
--
作者：
George, S.;Blay, J. Y.;Demetri, G. D.
目的：评估伊马替尼耐药/不耐受胃肠道间质瘤（GIST）患者的抗肿瘤活性，安全性，药代动力学和药效学的连续每日舒尼替尼给药，并评估早晨给药与晚上dosing.Patients和方法：在这个开放标签的II期研究，患者随机接受舒尼替尼37.5毫克/天的早晨或晚上给药。主要终点是临床获益率（CBR;完全缓解+部分缓解[PR] +疾病稳定[SD] ≥ 24周）。次要终点包括无进展生存期（PFS），总生存期（OS），安全性，药代动力学参数和血浆生物标志物levels.Results：60 61计划患者接受治疗（30每个剂量组），26完成了研究。总体而言，CBR为53%（95%精确CI，40-66）：8例患者（13%）达到客观PR; 24例（40%）达到SD >= 24周。中位PFS为34周（95% CI，24-49）;中位OS为107周（95% CI，72 -尚未计算）。大多数不良事件（AE）的严重程度为1级或2级，可通过剂量调整或标准干预进行管理。与获批的间歇给药方案相比，未发现明显的新AE。早晨和晚上给药的抗肿瘤活性和安全性通常相似。连续每日舒尼替尼给药达到并维持有效药物浓度，在周期内无额外蓄积。20和24周给药后血浆可溶性KIT水平较基线下降与较长的OS.Conclusion：对于伊马替尼耐药/不耐受GIST患者，连续每日舒尼替尼给药似乎是一种积极的替代给药策略，安全性可接受。(c)2009年由Elsevier Ltd.出版
Aims: To assess the antitumour activity, safety, pharmacokinetics and pharmacodynamics of continuous daily sunitinib dosing in patients with imatinib-resistant/intolerant gastrointestinal stromal tumour (GIST) and to assess morning dosing versus evening dosing.Patients and methods: In this open-label phase II study, patients were randomised to receive morning or evening dosing of sunitinib 37.5 mg/day. The primary end-point was clinical benefit rate (CBR; percent complete responses + partial responses [PRs] + stable disease [SD] >= 24 weeks). Secondary end-points included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters and plasma biomarker levels.Results: Sixty of 61 planned patients received treatment (30 per dosing group); 26 completed the study. overall, the CBR was 53% (95% exact CI, 40-66): eight patients (13%) achieved objective PRs; 24 (40%) achieved SD >= 24 weeks. Median PFS was 34 weeks (95% CI, 24-49); median OS was 107 weeks (95% CI, 72 - not yet calculable). Most adverse events (AEs) were of grade 1 or 2 in severity, and were manageable through dose modification or standard interventions. No new AEs were apparent compared with the approved intermittent dosing schedule. Antitumour activity and safety were generally similar with morning and evening dosing. Continuous daily sunitinib dosing achieved and sustained effective drug concentrations without additional accumulation across cycles. Decreases from baseline in plasma levels of soluble KIT after 20 and 24 weeks of dosing correlated with longer OS.Conclusion: For patients with imatinib-resistant/intolerant GIST, continuous daily sunitinib dosing appears to be an active alternative dosing strategy with acceptable safety. (c) 2009 Published by Elsevier Ltd.