An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma.
An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma.
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一项针对晚期肝细胞癌患者进行低剂量地西他滨治疗的开放标签、单臂、I/II 期研究。
DOI：
10.18632/oncotarget.3677
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发表时间：
2015-06-30
期刊：
影响因子：
--
通讯作者：
Han W
中科院分区：
文献类型：
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作者：
Mei Q;Chen M;Lu X;Li X;Duan F;Wang M;Luo G;Han W
我们进行了这项I/II期临床试验，以确定低剂量地西他滨为基础的治疗在预先治疗的晚期HCC患者中的安全性和有效性。晚期HCC患者符合条件。地西他滨的给药剂量为6 mg/m2/d，在28天周期的第1天至第5天静脉注射。根据其疾病进展状态给予其他治疗。研究目的是确定低剂量地西他滨的安全性、肝毒性、临床反应、无进展生存期（PFS）和药效学试验。入组了15例患者。观察到有利的不良事件和肝功能特征。最有益的反应是1个完全反应（CR），6个疾病稳定（SD）和8个疾病进展（PD）。治疗后的MRI肝脏扫描显示了独特和特定的特征。肝活检的免疫组化结果显示出显著的CTL应答。中位PFS为4个月（95%CI 1.7，7），与现有治疗方案相比具有优势。低剂量地西他滨治疗后，PBMC中DNMT 1表达减少，DNA低甲基化。基于低剂量地西他滨的治疗在晚期HCC患者中产生了有益的临床应答和有利的毒性特征。地西他滨的给药方案和基于肿瘤组织的药效学效应需要在未来的试验中进行前瞻性评价。
We conducted this phase I/II clinical trial to determine the safety and efficacy of lower-dose decitabine based therapy in pretreated patients with advanced HCC. Patients with advanced HCC were eligible. The administered dose of decitabine was 6 mg/m2/d intravenously on days 1 to 5 of a 28-day cycle. Additional therapies were given based on their disease progression status. The endpoint was to ensure the safety, hepatotoxicity, clinical responses, progression-free survival (PFS) and pharmacodynamics assay of lower-dose decitabine. Fifteen patients were enrolled. The favorable adverse events and liver function profiles were observed. The most beneficial responses were 1 complete response (CR), 6 stable disease (SD) and 8 progressive disease (PD). MRI liver scans post-treatment indicated a unique and specific characteristic. The immunohistochemistry result from the liver biopsy exhibited noteworthy CTL responses. Median PFS was 4 months (95% CI 1.7, 7), comparing favorably with existing therapeutic options. Expression decrement of DNMT1 and global DNA hypomethylation were observed in PBMCs after lower-dose decitabine treatment. The lower-dose decitabine based treatment resulted in beneficial clinical response and favorable toxicity profiles in patients with advanced HCC. The prospective evaluations of decitabine administration schemes and tumor tissue-based pharmacodynamics effect are warranted in future trials.