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

// Qian Mei 1,2,* , Meixia Chen 1,2,* , Xuechun Lu 1,2,* , Xiang Li 1,2 , Feng Duan 3 , Maoqiang Wang 3 , Guangbin Luo 1,4,* and Weidong Han 1,2 , * 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 Correspondence to: 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 Abstract 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.