Oberstein Paul E, Saif Muhammad Wasif
Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, New York, NY, USA.
JOP. 2011 Jul 8;12(4):358-61.
Pancreatic neuroendocrine tumors represent a small percentage of all pancreatic tumors (1.3%) but their incidence is rising. Prior to 2011, the only approved agent for unresectable disease was streptozicin (often used in combination with doxorubicin) but the efficacy of this drug is in question and there had not been any new drugs approved for this disease in more than 20 years. Recently there has been new excitement for the treatment of advanced neuroendocrine tumors including those of the pancreas (pNET) with FDA approval of 2 new agents in 2011. One of these agents was everolimus, an mTOR inhibitor, which was approved on the basis of a landmark phase III study (RADIANT-3). At the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, several abstracts were presented reviewing novel agents in the treatment of advanced NET. Three abstracts looked at characteristics of patients treated on the RADIANT-3 study and looked at the role of prior chemotherapy use (Abstract #4103), somatostatin analog use (Abstract #4010), and updated safety data (Abstract #4009) from this trial. Additionally, an abstract was presented (Abstract 4008) looking at updated data from the other targeted agent approved for advanced pNET, sunitinib, a multi-tyrosine kinase inhibitor, which demonstrated improvement in progression-free survival compared to placebo. Novel agents were also presented, including a phase II trial looking at the combination of sorafenib and bevacizumab (Abstract #4113), and a phase I trial looking at a novel somatostatin analog, pasireotide, in combination with everolimus (Abstract #4120) The authors review and summarize these abstracts in this article.
胰腺神经内分泌肿瘤在所有胰腺肿瘤中占比很小(1.3%),但其发病率正在上升。2011年之前,唯一被批准用于不可切除疾病的药物是链脲霉素(常与阿霉素联合使用),但这种药物的疗效存在疑问,并且20多年来一直没有针对该疾病的新药获批。最近,随着2011年美国食品药品监督管理局(FDA)批准了2种新药物,晚期神经内分泌肿瘤(包括胰腺神经内分泌肿瘤,pNET)的治疗出现了新的热潮。其中一种药物是依维莫司,一种mTOR抑制剂,它是基于一项具有里程碑意义的III期研究(RADIANT-3)获批的。在2011年美国临床肿瘤学会(ASCO)年会上,有几篇摘要介绍了晚期神经内分泌肿瘤治疗中的新型药物。三篇摘要研究了RADIANT-3研究中患者的特征,以及既往化疗使用情况(摘要#4103)、生长抑素类似物使用情况(摘要#4010)和该试验的最新安全性数据(摘要#4009)。此外,还有一篇摘要(摘要4008)介绍了另一种获批用于晚期pNET的靶向药物舒尼替尼(一种多酪氨酸激酶抑制剂)的最新数据,该药物与安慰剂相比,无进展生存期有所改善。还介绍了新型药物,包括一项关于索拉非尼和贝伐单抗联合使用的II期试验(摘要#4113),以及一项关于新型生长抑素类似物帕西瑞肽与依维莫司联合使用的I期试验(摘要#4120)。作者在本文中对这些摘要进行了回顾和总结。