@article{a4923ad6fb494e198198820f109cc0a1,
title = "Phase Ib/II study of safety and efficacy of low-dose decitabine-primed chemoimmunotherapy in patients with drug-resistant relapsed/refractory alimentary tract cancer",
abstract = "The pressing need for improved therapeutic outcomes provides a good rationale for identifying effective strategies for alimentary tract (AT) cancer treatment. The potential re-sensitivity property to chemo- and immunotherapy of low-dose decitabine has been evident both preclinically and in previous phase I trials. We conducted a phase Ib/II trial evaluating low-dose decitabine-primed chemoimmunotherapy in patients with drug-resistant relapsed/refractory (R/R) esophageal, gastric or colorectal cancers. Forty-five patients received either the 5-day decitabine treatment with subsequent readministration of the previously resistant chemotherapy (decitabine-primed chemotherapy, D-C cohort) or the aforementioned regimen followed by cytokine-induced killer cells therapy (D-C and cytokine-induced killer [CIK] cell treatment, D-C + CIK cohort) based on their treatment history. Grade 3 to 4 adverse events (AEs) were reported in 11 (24.4%) of 45 patients. All AEs were controllable, and no patient experienced a treatment-related death. The objective response rate (ORR) and disease control rate (DCR) were 24.44% and 82.22%, respectively, including two patients who achieved durable complete responses. Clinical response could be associated with treatment-free interval and initial surgical resection history. ORR and DCR reached 28% and 92%, respectively, in the D-C + CIK cohort. Consistently, the progression-free survival (PFS) of the D-C + CIK cohort compared favorably to the best PFS of the pre-resistant unprimed therapy (p = 0.0001). The toxicity and ORRs exhibited were non-significantly different between cancer types and treatment cohort. The safety and efficacy of decitabine-primed re-sensitization to chemoimmunotherapy is attractive and promising. These data warrant further large-scale evaluation of drug-resistant R/R AT cancer patients with advanced stage disease.",
keywords = "alimentary tract cancer, chemoimmunotherapy, drug resistance, hypomethylation agent, relapsed/refractory",
author = "Meixia Chen and Jing Nie and Yang Liu and Xiang Li and Yan Zhang and Brock, {Malcolm V.} and Kaichao Feng and Zhiqiang Wu and Xiaolei Li and Lu Shi and Suxia Li and Mingzhou Guo and Qian Mei and Weidong Han",
note = "Funding Information: Key words: alimentary tract cancer, relapsed/refractory, hypomethylation agent, drug resistance, chemoimmunotherapy Abbreviations: AEs: adverse events; AT: alimentary tract; BOR: best overall response; 95% CI: 95% confidence interval; CIK: cytokine-induced killer; CR: complete response; CRC: colorectal cancer; CT: computed tomography; CTCAE: the U.S. National Cancer Institute Common Toxicity Criteria for Adverse Events; DCR: disease control rate; EC: esophageal cancer; ECOG: Eastern Cooperative Oncologic Group; GC: gastric cancer; HMA: hypomethylating agents; ORR: objective response rate; OS: overall survival; PD: progressive disease; PFS: progression-free survival; PR: partial response; RECIST: the Response Evaluation Criteria in Solid Tumors; SD: stable disease. Additional Supporting Information may be found in the online version of this article. Conflict of interest: The authors declare that they have no potential conflicts of interest. †M.C., J.N., and Y.L. contributed equally to this work Grant sponsor: National Key R&D Program of China; Grant numbers: 2016YFC1303504 and 2016YFC1303501; Grant sponsor: National Natural Science Foundation of China; Grant numbers: 81773248, 81572914, 31671338 and 81230061 DOI: 10.1002/ijc.31531 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. History: Received 3 Nov 2017; Accepted 29 Mar 2018; Online 16 Apr 2018 Correspondence to: Weidong Han, Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, HaiDian District, Beijing 100853, People{\textquoteright}s Republic of China, Tel.: 186-10-6693-7463, Fax: 186-10-6693-7516, E-mail: hanwdrsw69@ yahoo.com; or Qian Mei, Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Hai-Dian District, Beijing 100853, People{\textquoteright}s Republic of China, Tel.: 186-10-6693-7917, Fax: 186-10-6693-7516, E-mail: meiqnn@hotmail.com Publisher Copyright: {\textcopyright} 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC",
year = "2018",
month = sep,
day = "15",
doi = "10.1002/ijc.31531",
language = "English (US)",
volume = "143",
pages = "1530--1540",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "6",
}