Role of Surgery Combined with Kinase Inhibition in the Management of Gastrointestinal Stromal Tumor (GIST)
Role of Surgery Combined with Kinase Inhibition in the Management of Gastrointestinal Stromal Tumor (GIST)
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DOI：
10.1245/s10434-010-1053-9
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发表时间：
2010-10-01
影响因子：
3.7
通讯作者：
Eisenberg, Burton
中科院分区：
文献类型：
--
作者：
Hohenberger, Peter;Eisenberg, Burton
背景手术是原发性胃肠道间质瘤（GIST）的标准治疗方法;然而，手术切除往往不能治愈，特别是在大型GIST中。在肿瘤完全切除后五年，大约一半的治疗患者复发。伊马替尼是一种口服酪氨酸激酶抑制剂（TKI），是转移性或不可切除GIST患者的一线治疗药物。它在84%的患者中产生了持久的客观反应或稳定的疾病，并且耐受性良好。伊马替尼治疗晚期胃肠道间质瘤的疗效引起了人们对多种潜在的多模式治疗方法的兴趣，这些方法将联合收割机手术与全身治疗相结合。最近，一项大型、随机、III期、美国合作组试验比较了原发性GIST患者在原发性完全手术切除术后1年使用伊马替尼辅助治疗与安慰剂治疗，结果显示安慰剂组患者复发时间显著缩短。这导致伊马替尼在美国和欧洲批准用于这一新适应症。几项评估伊马替尼辅助治疗术后复发风险高的原发性GIST患者疗效的研究正在进行中;特别是两项大型欧洲研究预计将在不久的将来产生初步结果。伊马替尼的新辅助治疗也正在研究其对手术结果的影响，首次试验结果已公布。本文提供了关于手术、TKI治疗及其联合治疗在GIST管理中快速发展的作用的最新信息，以及与当前临床研究结果相关的进一步综述。
Background. Surgery is the standard treatment for primary, gastrointestinal stromal tumor (GIST); however, surgical resection often is not curative, particularly in large GIST. Five years after complete removal of their tumor, approximately half of treated patients relapse. Imatinib, an oral tyrosine kinase inhibitor (TKI), is first-line treatment in patients with metastatic or unresectable GIST. It has resulted in durable objective responses or stable disease in 84% of patients and is well tolerated. The efficacy of imatinib in advanced GIST has created interest in a variety of potential multimodal approaches to management that combine surgery with systemic therapy.Results. Recently, a large, randomized, Phase III, US cooperative group trial that compared adjuvant imatinib, for I year after primary complete surgical resection, with placebo in primary GIST, reported a significantly shorter time to relapse for those in the placebo group. This led to the approval of imatinib for this new indication in the US and Europe. Several studies evaluating the efficacy of adjuvant imatinib in patients with primary GIST who are at high risk for postoperative relapse are ongoing; in particular two large European studies are expected to yield preliminary results in the near future. Neoadjuvant therapy with imatinib is also being investigated for its effect on surgical outcomes, with first trial results reported.Conclusion. This article provides an update on the rapidly evolving role of surgery, treatment with TKI therapy, and their combination in the management of GIST as well as further reviews pertinent to current clinical research findings.