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.
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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)
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Chemical References |
- Antimetabolites, Antineoplastic
- Decitabine
- DNA Modification Methylases
- DNA (Cytosine-5-)-Methyltransferase 1
- DNA (Cytosine-5-)-Methyltransferases
- DNMT1 protein, human
- Azacitidine
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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
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