Purpose

The role of streptozocin-based chemotherapy (STZ CTx) in advanced, well-differentiated pancreatic neuroendocrine tumours (PanNET) and the best sequence of treatments in advanced PanNET are unclear. We examined the outcomes after STZ CTx in patients who had been selected according to the current therapeutic guidelines.

Methods

Data from 50 PanNET patients consecutively treated with STZ CTx between 2010 and 2018 were analysed. The endpoints of the study were the objective-response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

STZ CTx was the first-line treatment in 54% of patients. The PanNET grades were as follows: 6% G1, 88% G2, and 6% well-differentiated G3. The ORR was 38%. Stable disease was the best response in 38% of patients and 24% showed progressive disease. Treatment was discontinued because of toxicity in one patient. Median PFS and OS were 12 (95% confidence interval (CI), 8.5–15.5) and 38 months (95% CI, 20.4–55.6), respectively. In the Kaplan-Meier analysis, the median OS was 89 months (95% CI, 34.9–143.1) for STZ CTx as first-line therapy compared with 22 months (95% CI, 19.3–24.7; p = 0.001, log-rank test) for subsequent lines. Bone metastases negatively impacted survival (HR, 2.71, p = 0.009, univariate analysis, HR, 2.64, p = 0.015, multivariate analysis, and Cox regression).

Conclusions

In patients selected according to current guidelines, PFS, and OS after STZ CTx were lower than previously reported, whereas ORR was unchanged. First-line treatment was positively associated with OS and the presence of bone metastases was negatively associated with OS. Pre-treatment with targeted or peptide-receptor radionuclide therapy did not alter ORR, PFS, or OS.

中文翻译：

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靶向治疗时代胰腺神经内分泌肿瘤的链脲佐菌素/5-氟尿嘧啶化疗

目的

基于链脲佐菌素的化疗 (STZ CTx) 在晚期高分化胰腺神经内分泌肿瘤 (PanNET) 中的作用以及晚期 PanNET 中的最佳治疗顺序尚不清楚。我们检查了根据当前治疗指南选择的患者 STZ CTx 后的结果。

方法

分析了 2010 年至 2018 年间连续接受 STZ CTx 治疗的 50 名 PanNET 患者的数据。研究的终点是客观反应率（ORR）、无进展生存期（PFS）和总生存期（OS）。

结果

STZ CTx 是 54% 患者的一线治疗。PanNET 等级如下：6% G1、88% G2 和 6% 高分化 G3。ORR 为 38%。在 38% 的患者中，病情稳定是最好的反应，24% 的患者表现出疾病进展。由于一名患者出现毒性而停止治疗。中位 PFS 和 OS 分别为 12（95% CI，8.5-15.5）和 38 个月（95% CI，20.4-55.6）。在 Kaplan-Meier 分析中，STZ CTx 作为一线治疗的中位 OS 为 89 个月（95% CI，34.9-143.1），而 STZ CTx 的中位 OS 为 22 个月（95% CI，19.3-24.7；p  = 0.001，对数秩测试）用于后续行。骨转移对生存产生负面影响（HR，2.71，p  = 0.009，单变量分析，HR，2.64，p = 0.015，多变量分析和 Cox 回归）。

结论

在根据当前指南选择的患者中，STZ CTx 后的 PFS 和 OS 低于先前报道的，而 ORR 没有变化。一线治疗与 OS 呈正相关，骨转移与 OS 呈负相关。用靶向或肽受体放射性核素治疗进行预处理不会改变 ORR、PFS 或 OS。