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晚期胃癌的当前及未来治疗方法

Current and Future Therapies for Advanced Gastric Cancer.

作者信息

Davidson Michael, Okines Alicia F C, Starling Naureen

机构信息

The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom.

The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom.

出版信息

Clin Colorectal Cancer. 2015 Dec;14(4):239-50. doi: 10.1016/j.clcc.2015.05.013. Epub 2015 Jun 6.

Abstract

The treatment of patients with advanced gastric cancer remains a challenging area of oncology. Extensive trials of differing chemotherapy regimens have yielded no international consensus on the optimal combination, and overall survival with chemotherapy alone remains poor. Recently an improved understanding of the molecular drivers of the disease has opened up promising new avenues of treatment through the use of biological targeted agents. The anti-HER2 monoclonal antibody trastuzumab was the first targeted agent to significantly prolong survival in the first-line treatment of a molecularly-selected subgroup of patients. More recently the anti-vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab has demonstrated a modest survival benefit in previously treated patients as both a monotherapy and in combination with chemotherapy. Immunotherapy and the use of checkpoint inhibitors are a further exciting area of development with promising preliminary results for the activity of the anti-Programmed Death 1 Receptor antibody pembrolizumab and ongoing trials of a number of immune-modulating agents. Continuing research to identify novel targets and therapies aims to make further incremental gains in survival. In this review we outline the evidence base supporting current chemotherapy regimens and describe the latest advances in the development and use of molecularly targeted and immune-modulating agents.

摘要

晚期胃癌患者的治疗仍然是肿瘤学中一个具有挑战性的领域。针对不同化疗方案的广泛试验并未就最佳组合达成国际共识,仅采用化疗的总体生存率仍然很低。最近,对该疾病分子驱动因素的进一步了解,通过使用生物靶向药物开辟了有前景的新治疗途径。抗HER2单克隆抗体曲妥珠单抗是首个在分子选择亚组患者的一线治疗中显著延长生存期的靶向药物。最近,抗血管内皮生长因子受体2单克隆抗体雷莫西尤单抗作为单一疗法以及与化疗联合使用时,在先前接受过治疗的患者中均显示出适度的生存获益。免疫疗法和检查点抑制剂的应用是另一个令人兴奋的发展领域,抗程序性死亡1受体抗体帕博利珠单抗的活性取得了有前景的初步结果,并且多项免疫调节剂正在进行试验。持续开展的旨在识别新靶点和新疗法的研究,目标是在生存率方面进一步取得渐进式提高。在本综述中,我们概述了支持当前化疗方案的证据基础,并描述了分子靶向药物和免疫调节剂研发与应用方面的最新进展。

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