PDF(Sci-hub)
Abstract：
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.
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.
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%).
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).
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.
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%).
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).
摘要：
有效的二线化疗方案在治疗晚期胆道癌（BTC）方面受到限制。Resminostat是一种口服组蛋白脱乙酰酶抑制剂。这种抑制剂增加了对氟尿嘧啶的敏感性,S-1的活性形式。在我的研究阶段,建议在S-1中添加瑞舒坦对预处理的BTC具有良好的疗效。本研究调查了瑞司诺司他加S-1在二线治疗BTC中的疗效和安全性。
在21天的周期内，患者被随机分配接受瑞舒坦或安慰剂（每天200mg，第1-5天和第8-12天）和S-1组（每天80-120mg，按体表面积计算，每天80-120mg，第1-14天）。主要终点是无进展生存期（PFS）。次要终点包括总生存期（OS），反应率（RR），疾病控制率（DCR），和安全。
在101名患者中，50人接受瑞舒坦+S-1，51人接受安慰剂+S-1。resminostat+S-1的平均PFS为2.9个月，与安慰剂+S-1为3.0个月（HR：1.154，95%CI：0.759-1.757，p=0.502）；中位OS为7.8个月。7.5个月,(HR：1.049，95%CI：0.653-1.684，p=0.834)；RR和DCR分别为6.0%和9.8%和70.0%vs.78.4%,分别。与治疗相关的不良事件（TrAE）≥3级（≥10％差异）在resminostat+S-1中发生的频率高于安慰剂+S-1，包括血小板计数降低（18.0％vs.2.0%）和食欲下降（16.0%vs.2.0%）。
Resminostat联合S-1治疗既不能改善BTC患者的PFS也不能改善OS。在S-1中添加瑞司诺司他与更高的TrAE发生率相关，但这些都是可控的（JapicCTI-183883）。
在21天的周期内，患者被随机分配接受瑞舒坦或安慰剂（每天200mg，第1-5天和第8-12天）和S-1组（每天80-120mg，按体表面积计算，每天80-120mg，第1-14天）。主要终点是无进展生存期（PFS）。次要终点包括总生存期（OS），反应率（RR），疾病控制率（DCR），和安全。
在101名患者中，50人接受瑞舒坦+S-1，51人接受安慰剂+S-1。resminostat+S-1的平均PFS为2.9个月，与安慰剂+S-1为3.0个月（HR：1.154，95%CI：0.759-1.757，p=0.502）；中位OS为7.8个月。7.5个月,(HR：1.049，95%CI：0.653-1.684，p=0.834)；RR和DCR分别为6.0%和9.8%和70.0%vs.78.4%,分别。与治疗相关的不良事件（TrAE）≥3级（≥10％差异）在resminostat+S-1中发生的频率高于安慰剂+S-1，包括血小板计数降低（18.0％vs.2.0%）和食欲下降（16.0%vs.2.0%）。
Resminostat联合S-1治疗既不能改善BTC患者的PFS也不能改善OS。在S-1中添加瑞司诺司他与更高的TrAE发生率相关，但这些都是可控的（JapicCTI-183883）。
