Phase I/II study of first-line combination therapy with sorafenib plus resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced hepatocellular carcinoma in east Asian patients
DC Field | Value | Language |
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dc.contributor.author | Tak, Won Young | - |
dc.contributor.author | Ryoo, Baek-Yeol | - |
dc.contributor.author | Lim, Ho Yeong | - |
dc.contributor.author | Kim, Do-Young | - |
dc.contributor.author | Okusaka, Takuji | - |
dc.contributor.author | Ikeda, Masafumi | - |
dc.contributor.author | Hidaka, Hisashi | - |
dc.contributor.author | Yeon, Jong-Eun | - |
dc.contributor.author | Mizukoshi, Eishiro | - |
dc.contributor.author | Morimoto, Manabu | - |
dc.contributor.author | Lee, Myung-Ah | - |
dc.contributor.author | Yasui, Kohichiroh | - |
dc.contributor.author | Kawaguchi, Yasunori | - |
dc.contributor.author | Heo, Jeong | - |
dc.contributor.author | Morita, Sojiro | - |
dc.contributor.author | Kim, Tae-You | - |
dc.contributor.author | Furuse, Junji | - |
dc.contributor.author | Katayama, Kazuhiro | - |
dc.contributor.author | Aramaki, Takeshi | - |
dc.contributor.author | Hara, Rina | - |
dc.contributor.author | Kimura, Takuya | - |
dc.contributor.author | Nakamura, Osamu | - |
dc.contributor.author | Kudo, Masatoshi | - |
dc.date.available | 2020-11-02T06:50:23Z | - |
dc.date.issued | 2018-12 | - |
dc.identifier.issn | 0167-6997 | - |
dc.identifier.issn | 1573-0646 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2860 | - |
dc.description.abstract | Purpose: Resminostat is an oral inhibitor of class I, IIB, and IV histone deacetylases. This phase I/II study compared the safety and efficacy of resminostat plus sorafenib versus sorafenib monotherapy as first-line therapy for advanced hepatocellular carcinoma (HCC). Experimental design: In phase I, resminostat (400mg or 600mg/day on days 1 to 5 every 14days) was administered with sorafenib (800mg/day for 14days) to determine the recommended dose for phase II. In phase II, patients were randomized (1:1) to sorafenib monotherapy or resminostat plus sorafenib. The primary endpoint was time-to-progression (TTP). Results: Nine patients (3: 400mg, 6: 600mg) were enrolled in phase I, and the recommended dose of resminostat was determined to be 400mg/day. Then 170 patients were enrolled in phase II. Median TTP/overall survival (OS) were 2.8/14.1months with monotherapy versus 2.8/11.8months with combination therapy (Hazard Ratio [HR]: 0.984, p=0.925/HR: 1.046, p=0.824). The overall incidence of adverse events was similar in both groups (98.8% versus 100.0%). However, thrombocytopenia Grade 3 was significantly more frequent in the combination therapy group (34.5% versus 2.4%, p<0.001). Subgroup analysis revealed that median TTP/OS was 1.5/6.9months for monotherapy versus 2.8/13.1months for combination therapy (HR: 0.795, p=0.392/HR: 0.567, p=0.065) among patients with a normal-to-high baseline platelet count ( 150x10(3)/mm(3)). Conclusions: In patients with advanced HCC, first-line therapy with resminostat at the recommended dose plus sorafenib showed no significant efficacy advantage over sorafenib monotherapy. | - |
dc.format.extent | 13 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Kluwer Academic Publishers | - |
dc.title | Phase I/II study of first-line combination therapy with sorafenib plus resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced hepatocellular carcinoma in east Asian patients | - |
dc.type | Article | - |
dc.publisher.location | 네델란드 | - |
dc.identifier.doi | 10.1007/s10637-018-0658-x | - |
dc.identifier.scopusid | 2-s2.0-85053437981 | - |
dc.identifier.wosid | 000450005200011 | - |
dc.identifier.bibliographicCitation | Investigational New Drugs, v.36, no.6, pp 1072 - 1084 | - |
dc.citation.title | Investigational New Drugs | - |
dc.citation.volume | 36 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 1072 | - |
dc.citation.endPage | 1084 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | ADVANCED SOLID TUMORS | - |
dc.subject.keywordPlus | JAPANESE PATIENTS | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | TRIALS | - |
dc.subject.keywordAuthor | Hepatocellular carcinoma | - |
dc.subject.keywordAuthor | HDAC | - |
dc.subject.keywordAuthor | Resminostat | - |
dc.subject.keywordAuthor | Sorafenib | - |
dc.subject.keywordAuthor | Systemic chemotherapy | - |
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