A clinical trial with valproic acid and hydralazine in combination with gemcitabine and cisplatin followed by doxorubicin and dacarbazine for advanced hepatocellular carcinoma

Yao Chung Liu, Chien Wei Su, Po Shen Ko, Rheun Chuan Lee, Chia Jen Liu, Yi Hsiang Huang, Jyh Pyng Gau, Jin Hwang Liu*

*此作品的通信作者

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

Background: Survival benefit from chemotherapy in advanced hepatocellular carcinoma (HCC) was limited till now. New chemoregimens with cytotoxicity modulators were explored to improve efficacy. Chemotherapy modulated with valproic acid (VA) as a deacetylation inhibitor of histone and DNA damage response proteins, and hydralazine (HZ) as a DNA hypomethylating agent, hypothetically suppressing DNA repair, were used in phase II trial here for advanced HCC. Methods: Between July 2008 and March 2016, patients with chemo-naive advanced HCC, regardless of previous sorafenib treatment, not amenable to local therapy and with Child Pugh score ≤7, were treated with VA (200 mg thrice per day) and HZ (12.5 mg twice per day) in conjunction with gemcitabine and cisplatin (GCGG): gemcitabine (1000 mg/m2, D1; 800 mg/m2 D8, 15) and cisplatin (70 mg/m2, D1) every 28 days till disease progression and then with Dox-DTIC: doxorubicin (45 mg/m2) and dacarbazine (450 mg/m2) every 28 days. The primary endpoint was overall survival (OS); the secondary endpoints were safety, progression-free survival (PFS) and response rate (RR). Results: Thirty-seven patients with 16 sorafenib-experienced, underwent GCGG treatment, and 30 of them underwent the following Dox-DTIC treatment. The median OS was 14.6 months (95% confidence interval: 6.0–23.1). The median PFSs for patients treated with VA- and HZ-combined GCGG and Dox-DTIC were 3.7 and 4.2 months, respectively; the RRs were 10/37 (27.0%) and 7/30 (23.3%); and grade 3/4 neutropenia were 54% and 51%. However, there were no chemotherapy-related deaths. Conclusion: VA- and HZ-combined sequential chemotherapy was effective in advanced HCC with manageable toxicities.

原文English
期刊Asia-Pacific Journal of Clinical Oncology
DOIs
出版狀態Accepted/In press - 2020

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