An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma

作者：Mei, Qian; Chen, Meixia; Lu, Xuechun; Li, Xiang; Duan, Feng; Wang, Maoqiang; Luo, Guangbin; Han, Weidong^*

来源：Oncotarget, 2015, 6(18): 16698-16711.

DOI：10.18632/oncotarget.3677

• decitabine
• lower dose
• advanced hepatocellular carcinoma
• hepatotoxicity
• phase I/II

Purpose: 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.
Experimental Design: Patients with advanced HCC were eligible. The administered dose of decitabine was 6 mg/m(2)/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.
Results: 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.
Conclusion: 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.

• 出版日期2015-6-30
• 单位中国人民解放军总医院