PMID- 26105599 OWN - NLM STAT- MEDLINE DCOM- 20160421 LR - 20220331 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 26 IP - 8 DP - 2015 Aug TI - Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. PG - 1766-71 LID - 10.1093/annonc/mdv237 [doi] AB - BACKGROUND: Chidamide is a novel benzamide type of subtype-selective histone deacetylase (HDAC) inhibitor with unique mechanisms of action compared with marketed HDAC inhibitors. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL) in Chinese population. PATIENTS AND METHODS: Patients with relapsed or refractory PTCL of different subtypes received chidamide of 30 mg orally twice per week. The primary end point was overall response rate (ORR). Responding patients should be confirmed at least 4 weeks after the criteria of the response were first met, and were reviewed by an independent review committee. RESULTS: Eighty-three patients were enrolled and 79 patients with eligible PTCL histology were for efficacy assessments. Patients enrolled over 10% were with subtypes of PTCL not otherwise specified (34%), anaplastic large-cell lymphoma (22%), extranodal natural killer (NK)/T-cell lymphoma, nasal type (20%), or angioimmunoblastic T-cell lymphoma (AITL, 13%). The ORR was 28% (22 of 79) including 14% (11 of 79) with complete response/unconfirmed complete response (CR/CRu). Median progression-free survival and overall survival were 2.1 and 21.4 months, respectively. AITL patients tended to have higher ORR (50%) and CR/CRu rate (40%), as well as more durable responses, to chidamide treatment. Most adverse events (AEs) were grade 1 or 2, and AEs >/=grade 3 that occurred in >/=10% patients were thrombocytopenia (22%), leucopenia (13%) and neutropenia (11%), respectively. CONCLUSION: Chidamide represents a novel oral benzamide class of HDAC inhibitor with significant single-agent activity and manageable toxicity in relapsed or refractory PTCL, and provides a much needed treatment option in this indication in China. Results led to China Food and Drug Administration approval of chidamide in this indication. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Shi, Y AU - Shi Y AD - Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing syuankai@cicams.ac.cn. FAU - Dong, M AU - Dong M AD - Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing. FAU - Hong, X AU - Hong X AD - Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai. FAU - Zhang, W AU - Zhang W AD - Department of Lymphoma, 307 Hospital of PLA, Beijing. FAU - Feng, J AU - Feng J AD - Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing. FAU - Zhu, J AU - Zhu J AD - Department of Medical Oncology, Beijing Caner Hospital, Beijing. FAU - Yu, L AU - Yu L AD - Department of Hematology, Chinese PLA General Hospital, Beijing. FAU - Ke, X AU - Ke X AD - Department of Hematology, Peking University Third Hospital, Beijing. FAU - Huang, H AU - Huang H AD - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou. FAU - Shen, Z AU - Shen Z AD - Department of Hematology, Ruijin Hospital/Medical College, Shanghai Jiao Tong University, Shanghai. FAU - Fan, Y AU - Fan Y AD - Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou. FAU - Li, W AU - Li W AD - Department of Hematology, the First Hospital, Jilin University, Changchun. FAU - Zhao, X AU - Zhao X AD - Department of Hematology, Xiangya Hospital Central South University, Changsha. FAU - Qi, J AU - Qi J AD - Department of Lymphoma, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin. FAU - Huang, H AU - Huang H AD - Department of Hematology, the First Affiliated Hospital, Zhejiang University, Hangzhou. FAU - Zhou, D AU - Zhou D AD - Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing. FAU - Ning, Z AU - Ning Z AD - Chipscreen Biosciences Ltd, Shenzhen, China. FAU - Lu, X AU - Lu X AD - Chipscreen Biosciences Ltd, Shenzhen, China. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150623 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Aminopyridines) RN - 0 (Antineoplastic Agents) RN - 0 (Benzamides) RN - 0 (Histone Deacetylase Inhibitors) RN - 87CIC980Y0 (N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide) SB - IM MH - Adult MH - Aged MH - Aminopyridines/*therapeutic use MH - Antineoplastic Agents/*therapeutic use MH - Benzamides/*therapeutic use MH - Disease-Free Survival MH - Enteropathy-Associated T-Cell Lymphoma/drug therapy MH - Female MH - Histone Deacetylase Inhibitors/*therapeutic use MH - Humans MH - Leukopenia/chemically induced MH - Lymphoma, Extranodal NK-T-Cell/drug therapy MH - Lymphoma, Large-Cell, Anaplastic/drug therapy MH - Lymphoma, T-Cell, Cutaneous/drug therapy MH - Lymphoma, T-Cell, Peripheral/*drug therapy MH - Male MH - Middle Aged MH - Mycosis Fungoides/drug therapy MH - Neoplasm Recurrence, Local/*drug therapy MH - Neutropenia/chemically induced MH - Skin Neoplasms/drug therapy MH - Thrombocytopenia/chemically induced MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - HDAC inhibitor OT - T-cell lymphoma OT - chidamide OT - epigenetic OT - pivotal trial EDAT- 2015/06/25 06:00 MHDA- 2016/04/22 06:00 CRDT- 2015/06/25 06:00 PHST- 2015/03/29 00:00 [received] PHST- 2015/05/11 00:00 [accepted] PHST- 2015/06/25 06:00 [entrez] PHST- 2015/06/25 06:00 [pubmed] PHST- 2016/04/22 06:00 [medline] AID - S0923-7534(19)31861-7 [pii] AID - 10.1093/annonc/mdv237 [doi] PST - ppublish SO - Ann Oncol. 2015 Aug;26(8):1766-71. doi: 10.1093/annonc/mdv237. Epub 2015 Jun 23.