New paradigms in gastrointestinal stromal tumour management
New paradigms in gastrointestinal stromal tumour management
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DOI：
10.1093/annonc/mdp075
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发表时间：
2009-05-01
影响因子：
50.5
通讯作者：
Blay, J. -Y.
中科院分区：
文献类型：
--
作者：
Blay, J. -Y.
背景：靶向药物改善了晚期胃肠道间质瘤（GIST）患者的预后。许多患者对甲磺酸伊马替尼一线治疗表现出不耐受或耐药。舒尼替尼苹果酸盐是批准用于治疗晚期伊马替尼难治性GIST.Design的多国：本文回顾了反应伊马替尼和舒尼替尼在临床试验中报告在晚期GIST和讨论的效果突变状态对治疗反应;在GIST治疗的治疗进展也进行了审查。伊马替尼400 mg/天已显示出对晚期GIST的一线治疗有效性，尤其是在KIT 11号外显子突变患者中。舒尼替尼50 mg/天（给药方案4/2）已证明在伊马替尼难治性GIST中的有效性和耐受性，包括将从临床试验中排除的患者。在一项回顾性研究中，与KIT 11号外显子突变相比，舒尼替尼与原发性KIT 9号外显子突变和野生型GIST患者的中位总生存期延长相关。正在进行的研究，包括伊马替尼在辅助设置和使用有针对性的药物序列或组合，将进一步完善先进GIST.Conclusions的治疗途径：有针对性的治疗和更好地了解突变状态对患者反应的影响，将有助于优化在先进的GIST的结果。
Background: Targeted agents have improved the prognosis for patients with advanced gastrointestinal stromal tumours (GISTs). Many patients exhibit intolerance or resistance to first-line therapy with imatinib mesylate. Sunitinib malate is approved multinationally for the treatment of advanced imatinib-refractory GIST.Design: This article reviews responses to imatinib and sunitinib reported in clinical trials in advanced GIST and discusses the effect of mutational status on treatment responses; therapeutic developments in GIST treatment are also reviewed.Results: Imatinib 400 mg/day has shown efficacy for first-line treatment of advanced GIST, particularly in patients with KIT exon 11 mutations. Sunitinib 50 mg/day (Schedule 4/2) has demonstrated effectiveness and tolerability in imatinib-refractory GIST, including patients who would be excluded from clinical trials. Sunitinib is associated with longer median overall survival in patients with primary KIT exon 9 mutations and wild-type GIST compared with KIT exon 11 mutations in a retrospective study. Ongoing studies, including imatinib in the adjuvant setting and the use of targeted agents in sequence or in combination, will further refine the therapeutic pathway for advanced GIST.Conclusions: The availability of targeted therapies and greater knowledge of the effect of mutational status on patient responses will assist in optimising outcomes in advanced GIST.