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

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/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.

• Authors: Qian Mei, Meixia Chen, Xuechun Lu, Xiang Li, Feng Duan, Maoqiang Wang, Guangbin Luo, Weidong Han
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 18 Pg. 16698-711 (Jun 30 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25895027 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Decitabine
• DNA Modification Methylases
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases
• DNMT1 protein, human
• Azacitidine

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Azacitidine (adverse effects, analogs & derivatives, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy)
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases (biosynthesis)
• DNA Methylation (drug effects)
• DNA Modification Methylases (antagonists & inhibitors)
• Decitabine
• Disease-Free Survival
• Female
• Humans
• Liver Neoplasms (drug therapy)
• Male
• Middle Aged
• Treatment Outcome