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

Autor: Keigo Makino, Hiroshi Ishii, Akihito Tsuji, Masato Ozaka, Makoto Ueno, Shingo Kobayashi, Manabu Muto, Daisuke Sakai, Yoshito Komatsu, Masafumi Ikeda, Nobumasa Mizuno, Akira Fukutomi, Toshikazu Moriwaki, Yousuke Nakai, Masayuki Furukawa, Takeshi Kajiwara, Akio Katanuma, Chigusa Morizane, Yuji Negoro, Masahiro Tsuda, Satoshi Shimizu, Junji Furuse, Noriko Nemoto
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Cancer Research
medicine.medical_treatment
Phases of clinical research
Administration
Oral
Platinum Compounds
Hydroxamic Acids
Gastroenterology
Deoxycytidine
Placebos
chemistry.chemical_compound
0302 clinical medicine
Resminostat
Japan
Antineoplastic Combined Chemotherapy Protocols
Original Research
Body surface area
Sulfonamides
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Progression-Free Survival
Drug Combinations
Biliary Tract Neoplasms
Oncology
Fluorouracil
030220 oncology & carcinogenesis
Female
medicine.drug
Adult
medicine.medical_specialty
biliary tract cancers
Placebo
lcsh:RC254-282
Drug Administration Schedule
03 medical and health sciences
Young Adult
Double-Blind Method
Internal medicine
medicine
Humans
systemic chemotherapy
Radiology
Nuclear Medicine and imaging
Adverse effect
histone deacetylase inhibitor
Aged
Tegafur
Chemotherapy
business.industry
Clinical Cancer Research
Gemcitabine
Oxonic Acid
030104 developmental biology
chemistry
resminostat plus S‐1
business
Zdroj: Cancer Medicine, Vol 10, Iss 6, Pp 2088-2099 (2021)
Cancer Medicine
ISSN: 2045-7634
Popis: Purpose 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. Methods Patients were randomly assigned to receive resminostat or placebo (200 mg orally per day; days 1–5 and 8–12) and S‐1 group (80–120 mg orally per day by body surface area; days 1–14) over a 21‐day cycle. The primary endpoint was progression‐free survival (PFS). Secondary endpoints comprised overall survival (OS), response rate (RR), disease control rate (DCR), and safety. Results Among 101 patients enrolled, 50 received resminostat+S‐1 and 51 received placebo+S‐1. Median PFS was 2.9 months for resminostat+S‐1 vs. 3.0 months for placebo+S‐1 (HR: 1.154, 95% CI: 0.759–1.757, p = 0.502); median OS was 7.8 months vs. 7.5 months, respectively (HR: 1.049, 95% CI: 0.653–1.684, p = 0.834); the RR and DCR were 6.0% vs. 9.8% and 70.0% vs. 78.4%, respectively. Treatment‐related adverse events (TrAEs) of grade ≥ 3 occurring more frequently (≥10% difference) in the resminostat+S‐1 than in the placebo+S‐1 comprised platelet count decreased (18.0% vs. 2.0%) and decreased appetite (16.0% vs. 2.0%). Conclusions Resminostat plus S‐1 therapy improved neither PFS nor OS for patients with pre‐treated BTCs. Addition of resminostat to S‐1 was associated with higher incidence of TrAEs, but these were manageable (JapicCTI‐183883).
This randomized, placebo‐controlled, double‐blind study investigated the efficacy and safety of resminostat plus S‐1 as a second‐line therapy in patients with BTCs. This was the first randomized study to use S‐1, which is widely used in second‐line treatment for BTC patients in Japan, as an active comparator. The results showed that resminostat plus S‐1 prolonged neither PFS nor OS in comparison with placebo plus S‐1.
Databáze: OpenAIRE
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