Dept. of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Dept. of Radiology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany.
Eur J Cancer. 2015 Jul;51(10):1253-62. doi: 10.1016/j.ejca.2015.04.005. Epub 2015 Apr 29.
The role of systemic chemotherapy for pancreatic neuroendocrine tumours (pNET) is controversially discussed. Objective response rates (RR) reported for streptozocin (STZ)-based chemotherapy are variable and novel targeted drugs have recently been approved. However, the sequence of treatment remains unclear. We aimed to evaluate the efficacy of STZ plus 5-fluorouracil (STZ/5-FU) in a large pNET cohort.
Data from 96 pNET patients treated with STZ/5-FU were analysed retrospectively. Endpoints of the study were RR, time to tumour progression (TTP) and overall survival (OS).
Mean age of patients at the start of chemotherapy was 57.6years (range, 32.1-80.4). STZ/5-FU was the 1st line treatment in 56.3%. 11.5% had G1, 79.2% G2 and 6.3% G3 neoplasms. Baseline progression was evident in 74%. Objective response rate was 42.7%. 40.6% of patients showed stable disease as best response while 16.7% showed progressive disease. Treatment was discontinued due to toxicity in 16 patients. Median TTP and OS were 19.4 (95% confidence interval (CI), 13.6-25.2) and 54.8months (95% CI, 34.7-74.9), respectively. In Cox regression analysis, Ki67>15% was the only negative prognostic factor for TTP (hazard ratio (HR), 3.3; P<0.001), confirmed by multivariate analysis (HR, 6.7; P=0.001).
STZ/5-FU was associated with considerable RR. Treatment was associated with durable TTP especially in patients with Ki67-index of ⩽15%. These findings along with good tolerability strengthen the value of this two-drug chemotherapy for the management of unresectable pNET.
对于胰腺神经内分泌肿瘤（pNET），全身化疗的作用存在争议。基于链脲佐菌素（STZ）的化疗的客观缓解率（RR）报道结果不一，且新型靶向药物最近已获得批准。然而，治疗顺序仍不清楚。我们旨在评估大样本 pNET 患者中 STZ 联合 5-氟尿嘧啶（STZ/5-FU）的疗效。
回顾性分析了 96 例接受 STZ/5-FU 治疗的 pNET 患者的数据。该研究的终点为 RR、肿瘤进展时间（TTP）和总生存期（OS）。
化疗开始时患者的平均年龄为 57.6 岁（范围，32.1-80.4）。STZ/5-FU 是一线治疗的 56.3%。11.5%为 G1 级，79.2%为 G2 级，6.3%为 G3 级肿瘤。74%的患者基线时有进展。客观缓解率为 42.7%。40.6%的患者最佳缓解为疾病稳定，16.7%的患者为疾病进展。由于毒性，16 名患者停止了治疗。中位 TTP 和 OS 分别为 19.4（95%置信区间（CI），13.6-25.2）和 54.8 个月（95%CI，34.7-74.9）。在 Cox 回归分析中，Ki67>15%是 TTP 的唯一负预后因素（危险比（HR），3.3；P<0.001），这在多变量分析中得到了证实（HR，6.7；P=0.001）。
STZ/5-FU 与相当高的 RR 相关。治疗与持久的 TTP 相关，特别是在 Ki67 指数 ⩽15%的患者中。这些发现以及良好的耐受性增强了这种两药化疗治疗不可切除的 pNET 的价值。
