Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 426, Houston, Texas 77030, USA.
J Clin Endocrinol Metab. 2011 Dec;96(12):3741-9. doi: 10.1210/jc.2011-0666. Epub 2011 Oct 12.
Everolimus, an oral inhibitor of mammalian target of rapamycin, significantly prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET). Chromogranin A (CgA) and neuron-specific enolase (NSE) are considered general biomarkers of these tumors.
The objective of the study was to evaluate the prognostic value of CgA and NSE in patients with pNET treated with everolimus.
Patients with low- to intermediate-grade advanced pNET enrolled in two phase 2 studies [RAD001 in Advanced Neuroendocrine Tumors (RADIANT-1) and single institution phase II study at The University of Texas M. D. Anderson Cancer Center] received everolimus. Blood samples were collected and analyzed by a central laboratory at baseline and monthly thereafter. PFS and overall survival (OS) were evaluated in patients with elevated and nonelevated baseline CgA/NSE levels.
In RADIANT-1, elevated vs. nonelevated baseline CgA was associated with shorter median PFS (8.34 vs. 15.64 months; P = 0.03) and OS (16.95 months vs. not reached; P < 0.001). Elevated vs. nonelevated baseline NSE resulted in shorter median PFS (7.75 vs. 12.29 months; P = 0.01) and OS (13.96 vs. 24.90 months; P = 0.005). Median PFS was prolonged in patients with early CgA or NSE response (11.0 vs. 5.0 months) compared with those without early biomarker response. More patients with CgA (87 vs. 50%) or NSE (81 vs. 14%) response experienced tumor shrinkage compared with those without response. CgA response data from the single-institution phase II study at The University of Texas M. D. Anderson Cancer Center study are consistent with data from the RADIANT-1 study.
Elevated baseline CgA/NSE provided prognostic information on PFS and survival; early CgA/NSE responses are potential prognostic markers for treatment outcomes in patients with advanced pNET.
依维莫司是一种哺乳动物雷帕霉素靶蛋白的口服抑制剂，可显著延长晚期胰腺神经内分泌肿瘤（pNET）患者的无进展生存期（PFS）。嗜铬粒蛋白 A（CgA）和神经元特异性烯醇化酶（NSE）被认为是这些肿瘤的一般生物标志物。
本研究旨在评估 CgA 和 NSE 在接受依维莫司治疗的 pNET 患者中的预后价值。
参加两项 2 期研究[RAD001 在高级神经内分泌肿瘤（RADIANT-1）和德克萨斯大学 M. D. 安德森癌症中心单机构 2 期研究]的低至中分级晚期 pNET 患者接受依维莫司治疗。在基线和此后每月采集血液样本并由中央实验室进行分析。在基线 CgA/NSE 水平升高和不升高的患者中评估无进展生存期（PFS）和总生存期（OS）。
在 RADIANT-1 中，与基线 CgA 升高相比，CgA 升高与较短的中位 PFS（8.34 与 15.64 个月；P=0.03）和 OS（16.95 个月与未达到；P<0.001）相关。与基线 NSE 升高相比，NSE 升高导致较短的中位 PFS（7.75 与 12.29 个月；P=0.01）和 OS（13.96 与 24.90 个月；P=0.005）。与无早期生物标志物反应的患者相比，早期 CgA 或 NSE 反应的患者 PFS 延长（11.0 与 5.0 个月）。与无反应的患者相比，有 CgA（87%比 50%）或 NSE（81%比 14%）反应的患者肿瘤缩小更多。来自德克萨斯大学 M. D. 安德森癌症中心的单机构 2 期研究的 CgA 反应数据与 RADIANT-1 研究的数据一致。
基线 CgA/NSE 升高提供了 PFS 和生存的预后信息；早期 CgA/NSE 反应可能是晚期 pNET 患者治疗结果的潜在预后标志物。
