Clinical Research Papers:
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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Qian Mei1,2,*, Meixia Chen1,2,*, Xuechun Lu1,2,*, Xiang Li1,2, Feng Duan3, Maoqiang Wang3, Guangbin Luo1,4,* and Weidong Han1,2,*
1 Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China
2 Department of Bio-therapeutic, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China
3 Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, P. R. China
4 Department of Genetics and Genome Sciences, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
* These authors have contributed equally to this work
Weidong Han, email:
Guangbin Luo, email:
Keywords: decitabine, lower dose, advanced hepatocellular carcinoma, hepatotoxicity, phase I/II
Received: September 19, 2014 Accepted: March 04, 2015 Published: March 29, 2015
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/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.
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.
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