A randomized, double‐blind, phase II study of oral histone deacetylase inhibitor resminostat plus S‐1 versus placebo plus S‐1 in biliary tract cancers previously treated with gemcitabine plus platinum‐based chemotherapy

Effective second‐line chemotherapy options are limited in treating advanced biliary tract cancers (BTCs). Resminostat is an oral histone deacetylase inhibitor. Such inhibitors increase sensitivity to fluorouracil, the active form of S‐1. In the phase I study, addition of resminostat to S‐1 was suggested to have promising efficacy for pre‐treated BTCs. This study investigated the efficacy and safety of resminostat plus S‐1 in second‐line therapy for BTCs.

[1]  H. Katayama,et al.  Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: The FUGA-BT (JCOG1113) Randomized Phase III Clinical Trial. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  A. Maraveyas,et al.  ABC-06 | A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin / 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) che , 2019, Journal of Clinical Oncology.

[3]  E. Vasile,et al.  Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations. , 2019, European journal of cancer.

[4]  H. Ueno,et al.  Phase I study of resminostat, an HDAC inhibitor, combined with S-1 in patients with pre-treated biliary tract or pancreatic cancer , 2018, Investigational new drugs.

[5]  H. Eguchi,et al.  Randomized phase III study of gemcitabine, cisplatin plus S-1 (GCS) versus gemcitabine, cisplatin (GC) for advanced biliary tract cancer (KHBO1401-MITSUBA). , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[6]  B. Quesnel,et al.  Targeting MYC in multiple myeloma , 2017, Leukemia.

[7]  Bin Tean Teh,et al.  Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. , 2017, Cancer discovery.

[8]  H. Chang,et al.  Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin: retrospective analysis of 740 patients , 2017, Cancer Chemotherapy and Pharmacology.

[9]  K. Boberg,et al.  Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) , 2016, Nature Reviews Gastroenterology &Hepatology.

[10]  T. Takada,et al.  Biliary tract cancer registry in Japan from 2008 to 2013 , 2016, Journal of hepato-biliary-pancreatic sciences.

[11]  T. Tamura,et al.  A phase I study of resminostat in Japanese patients with advanced solid tumors , 2015, Cancer Chemotherapy and Pharmacology.

[12]  T. Utsunomiya,et al.  Role of histone deacetylase expression in intrahepatic cholangiocarcinoma. , 2012, Surgery.

[13]  N. Sasahira,et al.  Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine , 2012, Investigational New Drugs.

[14]  D. Cunningham,et al.  Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. , 2010, The New England journal of medicine.

[15]  Y. Gong,et al.  Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer. , 2009, Oncology reports.

[16]  Martin J Blaser,et al.  Infection, cancer and prevention: report of the 19th International Symposium of the Foundation for Promotion of Cancer Research. , 2006, Japanese journal of clinical oncology.

[17]  Y. Bang,et al.  Histone Deacetylase Inhibitors for Cancer Therapy , 2006, Epigenetics.

[18]  M. Shimizu,et al.  Thymidylate synthase predictive power is overcome by irinotecan combination therapy with S-1 for gastric cancer , 2004, British Journal of Cancer.

[19]  Edward Chu,et al.  Thymidylate synthase inhibitors as anticancer agents: from bench to bedside , 2003, Cancer Chemotherapy and Pharmacology.

[20]  G. Peters,et al.  Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. , 2002, Biochimica et biophysica acta.

[21]  Peter A. Jones,et al.  The fundamental role of epigenetic events in cancer , 2002, Nature Reviews Genetics.

[22]  G. Aherne,et al.  Comparison of thymidylate synthase (TS) protein up-regulation after exposure to TS inhibitors in normal and tumor cell lines and tissues. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.