Phase I study of resminostat, an HDAC inhibitor, combined with S-1 in patients with pre-treated biliary tract or pancreatic cancer

被引：21

作者：

Ikeda, Masafumi ^{[1
]}

Ohno, Izumi ^{[1
]}

Ueno, Hideki ^{[2
]}

Mitsunaga, Shuichi ^{[1
]}

Hashimoto, Yusuke ^{[1
]}

Okusaka, Takuji ^{[2
]}

Kondo, Shunsuke ^{[2
]}

Sasaki, Mitsuhito ^{[1
]}

Sakamoto, Yasunari ^{[2
]}

Takahashi, Hideaki ^{[1
]}

Hara, Rina ^{[3
]}

Kobayashi, Shingo ^{[3
]}

Nakamura, Osamu ^{[3
]}

Morizane, Chigusa ^{[2
]}

机构：

[1] Natl Canc Ctr Hosp East, Dept Hepatobiliary & Pancreat Oncol, 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan

[2] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Oncol, Tokyo, Japan

[3] Yakult Honsha Co Ltd, Pharmaceut Res & Dev Dept, Tokyo, Japan

来源：

INVESTIGATIONAL NEW DRUGS | 2019年 / 37卷 / 01期

关键词：

Biliary tract cancer; Histone deacetylase; Resminostat; S-1; Systemic cancer therapy; HISTONE DEACETYLASE INHIBITOR; THYMIDYLATE SYNTHASE; EXPRESSION; CHEMOTHERAPY; COMBINATION; THERAPY;

D O I：

10.1007/s10637-018-0634-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Resminostat is an oral hydroxamate inhibitor of class I, IIb, and IV histone deacetylases. S-1 is widely used to treat biliary tract cancer and pancreatic cancer in Japan. We performed a phase I study of resminostat combined with S-1 as second-line or later therapy in Japanese patients with biliary tract or pancreatic cancer. A total of 27 patients were enrolled. We determined the optimal regimen for resminostat/S-1 therapy in part 1, and investigated its safety and efficacy in part 2. In part 1, 17 patients were enrolled. One DLT (anorexia and stomatitis, respectively) occurred with each of regimens 2 and 3. In part 2, an additional 10 patients received regimen 3, which was selected in part 1. Regimen 3 was resminostat (200mg/day on Days 1 to 5 and Days 8 to 12: 5days on/2days off) plus S-1 (80-120mg/day according to body surface area on Days 1 to 14) repeated every 21days. A total of 16 patients (13 with biliary tract cancer and 3 with pancreatic cancer) received regimen 3 and it was well tolerated. The most frequent treatment-related adverse events were thrombocytopenia and anorexia (11 patients each, 69%). The disease control rate was 81.3% (84.6% for biliary tract cancer and 66.7% for pancreatic cancer, respectively). Median progression-free survival was 3.1months (5.5 and 2.3months), while median overall survival was 8.8months (10.2 and 4.7months). In conclusion, regimen 3 was well tolerated by patients with pre-treated biliary tract or pancreatic cancer.

引用

页码：109 / 117

页数：9