Background: This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin Yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC). Methods: A phase II single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1000mg/m2 and cisplatin 25mg/m2 on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity and time from SIRT to commencement of chemotherapy. Results: Total thirty-one patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1-8). The median OS was 13·6 months (95% CI: 5·4-21·6) for the intent-to-treat population. Amongst sixteen patients undergoing chemotherapy, the median OS was 21·6 months (95% CI: 7·3-25·2) and the median PFS was nine months (95% CI: 3·2-13·1). The response rate was 25% (95% CI: 3·8%-46·2%) and the disease control rate was 75% (95% CI: 53·8% -96·2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7-42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n=4), underlying treatment unrelated co-morbidities (n=2) and withdrawal of consent due to personal reasons (n=2). Conclusions: Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.


中文翻译：

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钇90树脂微球继以吉西他滨加顺铂治疗不可切除肝内胆管癌的选择性内部放射治疗：II期单臂多中心临床试验

背景：这项由研究者发起的临床试验旨在研究在不可切除的肝内胆管癌 (ICC) 中使用树脂钇-90 微球 (SIRT) 进行选择性内部放射治疗，然后进行标准化疗的疗效和安全性。方法：对不可切除的 ICC 患者（NCT02167711）进行了一项 II 期单臂多中心研究。以 120 Gy 的剂量对肿瘤进行 SIRT，然后在 21 天周期的第 1 天和第 8 天开始使用吉西他滨 1000mg/m2 和顺铂 25mg/m2。主要终点是总生存期（OS），次要终点包括无进展生存期（PFS）、根据实体瘤反应评估标准1.1的反应率、毒性和从SIRT到开始化疗的时间。结果：总共筛选了 31 名患者，招募了 24 名患者。所有患者均完成了 SIRT，其中 16 人接受了后续化疗。化疗的中位周期为 5 个（范围：1-8）。意向治疗人群的中位 OS 为 13·6 个月（95% CI：5·4-21·6）。在接受化疗的 16 名患者中，中位 OS 为 21·6 个月（95% CI：7·3-25·2），中位 PFS 为 9 个月（95% CI：3·2-13·1）。缓解率为25%（95% CI：3·8%-46·2%），疾病控制率为75%（95% CI：53·8%-96·2%）。没有观察到新的安全信号，只有不到 10% 的患者患有 3 级或更高级别的治疗相关不良事件。从 SIRT 到化疗的中位时间为 29（范围：7-42）天。8 名患者因疾病进展迅速而无法接受化疗（n=4），潜在治疗无关的合并症（n = 2）和由于个人原因撤回同意（n = 2）。结论： SIRT 继以标准吉西他滨和顺铂化疗对不可切除的 ICC 是可行且有效的。需要进一步的研究来研究 SIRT 和化疗的最佳顺序。