PMID- 29663379 OWN - NLM STAT- MEDLINE DCOM- 20190204 LR - 20240330 IS - 1097-0215 (Electronic) IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 143 IP - 6 DP - 2018 Sep 15 TI - Phase Ib/II study of safety and efficacy of low-dose decitabine-primed chemoimmunotherapy in patients with drug-resistant relapsed/refractory alimentary tract cancer. PG - 1530-1540 LID - 10.1002/ijc.31531 [doi] AB - 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. CI - (c) 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. FAU - Chen, Meixia AU - Chen M AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Nie, Jing AU - Nie J AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Liu, Yang AU - Liu Y AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Li, Xiang AU - Li X AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Brock, Malcolm V AU - Brock MV AD - Department of Surgery, Johns Hopkins University, Baltimore, MD. FAU - Feng, Kaichao AU - Feng K AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Wu, Zhiqiang AU - Wu Z AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Li, Xiaolei AU - Li X AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Shi, Lu AU - Shi L AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Li, Suxia AU - Li S AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Guo, Mingzhou AU - Guo M AD - Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Mei, Qian AU - Mei Q AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Han, Weidong AU - Han W AUID- ORCID: 0000-0003-3207-3899 AD - Department of Molecular Biology and Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People's Republic of China. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180426 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 776B62CQ27 (Decitabine) SB - IM MH - Adenocarcinoma/drug therapy/immunology/secondary MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Squamous Cell/drug therapy/immunology/secondary MH - Cells, Cultured MH - Cohort Studies MH - Cytokine-Induced Killer Cells/drug effects/immunology/pathology MH - Decitabine/*therapeutic use MH - Digestive System/*drug effects/immunology/pathology MH - Digestive System Neoplasms/*drug therapy/immunology/pathology MH - Dose-Response Relationship, Drug MH - *Drug Resistance, Neoplasm MH - Female MH - Follow-Up Studies MH - Humans MH - *Immunotherapy MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/*drug therapy/immunology/pathology MH - Prognosis MH - *Salvage Therapy MH - Survival Rate PMC - PMC6099263 OTO - NOTNLM OT - alimentary tract cancer OT - chemoimmunotherapy OT - drug resistance OT - hypomethylation agent OT - relapsed/refractory EDAT- 2018/04/18 06:00 MHDA- 2019/02/05 06:00 PMCR- 2018/08/20 CRDT- 2018/04/18 06:00 PHST- 2017/11/03 00:00 [received] PHST- 2018/03/19 00:00 [revised] PHST- 2018/03/29 00:00 [accepted] PHST- 2018/04/18 06:00 [pubmed] PHST- 2019/02/05 06:00 [medline] PHST- 2018/04/18 06:00 [entrez] PHST- 2018/08/20 00:00 [pmc-release] AID - IJC31531 [pii] AID - 10.1002/ijc.31531 [doi] PST - ppublish SO - Int J Cancer. 2018 Sep 15;143(6):1530-1540. doi: 10.1002/ijc.31531. Epub 2018 Apr 26.