Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuan, Chaoyang District, Beijing, 100021, China.
Cancer Chemother Pharmacol. 2012 Jun;69(6):1413-22. doi: 10.1007/s00280-012-1847-5. Epub 2012 Feb 24.
Chidamide (CS055/HBI-8000) is a new benzamide class of histone deacetylase inhibitor with marked anti-tumor activity. This study reports the phase I results.
Patients with advanced solid tumors or lymphomas received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either twice (BIW) or three times (TIW) per week for 4 consecutive weeks every 6 weeks. Safety, characteristics of pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy were evaluated.
A total of 31 patients were enrolled. No DLTs were identified in the BIW cohorts up to 50 mg. DLTs were grade 3 diarrhea and vomiting in two patients in the TIW cohort at 50 mg, respectively. PK analysis revealed t(1/2) of 16.8-18.3 h, T(max) of 1-2 h in most cases, and a dose-related increase in C(max) and AUC. Significant induction of histone H3 acetylation in peripheral white blood cells was observed after a single dose of chidamide. Four patients with T-cell lymphomas and 1 patient with submandibular adenoid cystic carcinoma achieved a partial response.
Chidamide was generally well tolerated in patients with advanced solid tumors or lymphomas in the tested regimens. Favorable PK and PD profiles, as well as encouraging preliminary anti-tumor activity, were demonstrated.
西达本胺（CS055/HBI-8000）是一种新型的组蛋白去乙酰化酶抑制剂，具有显著的抗肿瘤活性。本研究报告了其 I 期临床试验结果。
患有晚期实体瘤或淋巴瘤的患者接受口服西达本胺 5、10、17.5、25、32.5 或 50mg，每周两次（BIW）或每周三次（TIW），连续 4 周，每 6 周为一个周期。评估安全性、药代动力学（PK）和药效学（PD）特征以及初步疗效。
共纳入 31 例患者。在 BIW 组中，最高剂量达 50mg 时未观察到剂量限制性毒性（DLT）。在 TIW 组中，50mg 剂量时分别有 2 例患者出现 3 级腹泻和呕吐。PK 分析显示，t(1/2)为 16.8-18.3 小时，大多数情况下 T(max)为 1-2 小时，且 C(max)和 AUC 呈剂量相关性增加。单次给药后，外周血白细胞中的组蛋白 H3 乙酰化明显增加。4 例 T 细胞淋巴瘤患者和 1 例颌下腺腺样囊性癌患者获得部分缓解。
在试验方案中，西达本胺在晚期实体瘤或淋巴瘤患者中总体耐受良好。显示出良好的 PK 和 PD 特征以及令人鼓舞的初步抗肿瘤活性。
