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01-06-2012 | Original Article

Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas

Authors: Mei Dong, Zhi-Qiang Ning, Pu-Yuan Xing, Jia-Lian Xu, Hai-Xiang Cao, Gui-Fang Dou, Zhi-Yun Meng, Yuan-Kai Shi, Xian-Ping Lu, Feng-Yi Feng

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2012

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Title: Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas
Authors: Mei Dong
Zhi-Qiang Ning
Pu-Yuan Xing
Jia-Lian Xu
Hai-Xiang Cao
Gui-Fang Dou
Zhi-Yun Meng
Yuan-Kai Shi
Xian-Ping Lu
Feng-Yi Feng
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1847-5

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