Publication: A phase i study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors
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Issued Date
2015-01-01
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15730646
01676997
01676997
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2-s2.0-84922071202
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Mahidol University
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SCOPUS
Bibliographic Citation
Investigational New Drugs. Vol.33, No.1 (2015), 225-232
Suggested Citation
Nuttapong Ngamphaiboon, Grace K. Dy, Wen Wee Ma, Yujie Zhao, Thanyanan Reungwetwattana, Dawn Depaolo, Yi Ding, William Brady, Gerald Fetterly, Alex A. Adjei A phase i study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors. Investigational New Drugs. Vol.33, No.1 (2015), 225-232. doi:10.1007/s10637-014-0174-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/36763
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A phase i study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors
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Abstract
© 2014 Springer Science+Business Media New York. Based on preclinical data demonstrating cytotoxic synergy between sorafenib and entinostat, a phase I study of this combination was conducted in patients with advanced solid tumors. Enrollment followed the traditional "3+3" dose escalation scheme. Entinostat was given orally once every 2 weeks, starting at a dose of 4 mg and escalating to 6 and 10 mg every 2 weeks. Sorafenib was administered as a continuous oral dose, escalating from 200 to 400 mg twice daily. A treatment cycle was 28 days. A total of 31 patients with advanced solid tumors were enrolled on the study. The three dose-limiting toxicities (DLTs) observed were grade 3 hand-foot syndrome, nausea/vomiting, and fatigue. MTD was not reached. The recommended phase II dose was defined as the full dose of the respective drugs administered individually. The most common grade 3-4 toxicities were muscle weakness (13 %), skin rash (10 %), fatigue (6 %), diarrhea (6 %), and hand-foot syndrome (3 %). One NSCLC patient achieved a partial response. Two patients (adenocarcinoma of GE junction and Hurthle cell carcinoma of the thyroid) were on the study for more than 9 months with stable disease. The combination of entinostat and sorafenib was well tolerated. Entinostat 10 mg orally once every 2 weeks in combination with sorafenib 400 mg orally twice daily, representing full single agent doses of each drug was identified as the recommended phase 2 dose (RP2D). These data support future clinical development of the combination of entinostat and sorafenib.