title: An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.|Department of Bio-therapeutic, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Mei
authors.affiliation: Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.|Department of Bio-therapeutic, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Meixia
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.|Department of Bio-therapeutic, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Xuechun
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.|Department of Bio-therapeutic, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Duan
authors.affiliation: Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Maoqiang
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.|Department of Genetics and Genome Sciences, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Guangbin
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.|Department of Bio-therapeutic, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D015254:DNA Modification Methylases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D001374:Azacitidine
keywords: advanced hepatocellular carcinoma; decitabine; hepatotoxicity; lower dose; phase I/II