{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:37:01Z","timestamp":1783445821327,"version":"3.54.6"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Asia-Pac J Clncl Oncology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between July 2008 and March 2016, patients with chemo\u2010naive advanced HCC, regardless of previous sorafenib treatment, not amenable to local therapy and with Child Pugh score \u22647, were treated with VA (200\u00a0mg thrice per day) and HZ (12.5\u00a0mg twice per day) in conjunction with gemcitabine and cisplatin (GCGG): gemcitabine (1000\u00a0mg\/m<jats:sup>2<\/jats:sup>, D1; 800\u00a0mg\/m<jats:sup>2<\/jats:sup> D8, 15) and cisplatin (70\u00a0mg\/m<jats:sup>2<\/jats:sup>, D1) every 28 days till disease progression and then with Dox\u2010DTIC: doxorubicin (45\u00a0mg\/m<jats:sup>2<\/jats:sup>) and dacarbazine (450\u00a0mg\/m<jats:sup>2<\/jats:sup>) every 28 days. The primary endpoint was overall survival (OS); the secondary endpoints were safety, progression\u2010free survival (PFS) and response rate (RR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010seven patients with 16 sorafenib\u2010experienced, underwent GCGG treatment, and 30 of them underwent the following Dox\u2010DTIC treatment. The median OS was 14.6 months (95% confidence interval: 6.0\u201323.1). The median PFSs for patients treated with VA\u2010 and HZ\u2010combined GCGG and Dox\u2010DTIC 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\u2010related deaths.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>VA\u2010 and HZ\u2010combined sequential chemotherapy was effective in advanced HCC with manageable toxicities.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ajco.13443","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T05:46:54Z","timestamp":1600840014000},"page":"19-27","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A clinical trial with valproic acid and hydralazine in combination with gemcitabine and cisplatin followed by doxorubicin and dacarbazine for advanced hepatocellular carcinoma"],"prefix":"10.1111","volume":"18","author":[{"given":"Yao\u2010Chung","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"School of Medicine National Yang\u2010Ming 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