Evidence map›Paper›PMID 30198057›Full record

Trial reportInvestigational new drugs2018

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.

Won Young Tak, Baek-Yeol Ryoo, Ho Yeong Lim, Do-Young Kim, Takuji Okusaka, Masafumi Ikeda, Hisashi Hidaka, Jong-Eun Yeon, Eishiro Mizukoshi, Manabu Morimoto and 13 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIComparative Study
PubMed Publisher
In one paragraph

Trial report in Investigational new drugs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025
    Review
  11. Review
  12. Review
  13. Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Epigenetic remodelling in human hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Won Young TakDivision of Gastroenterology and Hepatology, Department of Internal medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-Ro, Jung-Gu, Daegu, 41944, South Korea. wytak@knu.ac.kr.ORCID 0000-0002-1914-5141
Baek-Yeol RyooOncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Ho Yeong LimHematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.
Do-Young KimDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Takuji OkusakaDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Masafumi IkedaDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan.
Hisashi HidakaDepartment of Gastroenterology, Kitasato University Hospital, Kanagawa, Japan.
Jong-Eun YeonLiver Center, Korea University Guro Hospital, Seoul, South Korea.
Eishiro MizukoshiDepartment of Gastroenterology, Kanazawa University Hospital, Ishikawa, Japan.
Manabu MorimotoDepartment of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Kanagawa, Japan.
Myung-Ah LeeOncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Kohichiroh YasuiDepartment of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yasunori KawaguchiDepartment of Hepato-Biliary-Pancreatology, Saga-ken Medical Centre Koseikan, Saga, Japan.
Jeong HeoDepartment of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, South Korea.
Sojiro MoritaDepartment of Radiology, Kochi Health Sciences Center, Kochi, Japan.
Tae-You KimDepartment of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Junji FuruseDepartment of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Kazuhiro KatayamaDepartment of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Takeshi AramakiDivision of Interventional Radiology, Shizuoka Cancer Center, Shizuoka, Japan.
Rina HaraPharmaceutical Research and Development Department, Yakult Honsha Co., Ltd., Tokyo, Japan.
Takuya KimuraPharmaceutical Research and Development Department, Yakult Honsha Co., Ltd., Tokyo, Japan.
Osamu NakamuraPharmaceutical Research and Development Department, Yakult Honsha Co., Ltd., Tokyo, Japan.
Masatoshi KudoDepartment of Gastroenterology and Hepatology, Kindai University Hospital, Osaka, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeResminostat 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

designIn phase I, resminostat (400 mg or 600 mg/day on days 1 to 5 every 14 days) was administered with sorafenib (800 mg/day for 14 days) 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).

resultsNine patients (3: 400 mg, 6: 600 mg) were enrolled in phase I, and the recommended dose of resminostat was determined to be 400 mg/day. Then 170 patients were enrolled in phase II. Median TTP/overall survival (OS) were 2.8/14.1 months with monotherapy versus 2.8/11.8 months 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 1.5/6.9 months for monotherapy versus 2.8/13.1 months 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 (≥ 150 × 10

conclusionsIn patients with advanced HCC, first-line therapy with resminostat at the recommended dose plus sorafenib showed no significant efficacy advantage over sorafenib monotherapy.

Indexed as

Asian PeopleAdministration, OralAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, HepatocellularFemaleHistone Deacetylase InhibitorsHumansHydroxamic AcidsKaplan-Meier EstimateLiver NeoplasmsMaleNeoplasm StagingSorafenibSulfonamidesTreatment OutcomeHistone Deacetylase InhibitorsHydroxamic AcidsresminostatSorafenibSulfonamidesHDACHepatocellular carcinomaResminostatSorafenibSystemic chemotherapy

Identifiers

PMID30198057

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.