Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 69, Issue 6, Pages 1413-1422Publisher
SPRINGER
DOI: 10.1007/s00280-012-1847-5
Keywords
Chidamide; HDAC inhibitor; Phase I; Solid tumor; Lymphoma
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Funding
- Chinese National 863 Project [2008AA02Z303]
- National Prize for Small- and Middle-sized enterprises [04C26214420752]
- Significant Project in Biotech Field from Guangdong Province [2003A10903]
- Significant Project in Biotech Field from Shenzhen City [2005-K2-009]
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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.
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