UCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6BT, UK.
Expert Rev Anticancer Ther. 2011 Nov;11(11):1653-65. doi: 10.1586/era.11.145. Epub 2011 Sep 20.
Survival from pancreatic neuroendocrine tumors has not improved over the past two decades and, until recently, streptozocin was the last therapeutic agent approved for this malignancy. Everolimus blocks mTOR, which plays an integral role in cell growth, mitosis and angiogenesis. Abnormal PI3K-Akt/PKB-mTOR pathway signaling has been implicated in the pathogenesis of pancreatic neuroendocrine tumors. In a Phase III study, patients with low- and intermediate-grade advanced pancreatic neuroendocrine tumors were randomized to receive everolimus 10 mg/day or placebo. Median progression-free survival was significantly greater in patients treated with everolimus than placebo - 11 versus 4.6 months - and drug-related adverse events were consistent with the known side-effect profile of everolimus. Everolimus represents a significant treatment development for pancreatic neuroendocrine tumors.
过去二十年来，胰腺神经内分泌肿瘤患者的生存率并未得到改善，直到最近，链脲佐菌素才是这种恶性肿瘤批准的最后一种治疗药物。依维莫司可阻断 mTOR，mTOR 在细胞生长、有丝分裂和血管生成中起着重要作用。异常的 PI3K-Akt/PKB-mTOR 通路信号转导与胰腺神经内分泌肿瘤的发病机制有关。在一项 III 期研究中，低级别和中级别晚期胰腺神经内分泌肿瘤患者被随机分配接受依维莫司 10 mg/天或安慰剂治疗。与安慰剂相比，接受依维莫司治疗的患者中位无进展生存期显著延长（11 个月 vs. 4.6 个月），药物相关不良反应与依维莫司已知的副作用谱一致。依维莫司是胰腺神经内分泌肿瘤治疗的重大进展。
