title: Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.
abstract: Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China ; Department of Geriatric Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Hui
authors: H
authors: Fan
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China ; Department of Geriatric Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Xuechun
authors: X
authors: Lu
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Xiaohui
authors: X
authors: Wang
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China ; Department of Geriatric Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Yang
authors: Y
authors: Liu
authors: Department of Geriatric Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Bo
authors: B
authors: Guo
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Wenying
authors: W
authors: Zhang
authors: Department of Immunology, Institute of Basic Medicine, Medical College of PLA, Chinese PLA General Hospital, Beijing 100853, China.
authors: Jing
authors: J
authors: Nie
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Kaichao
authors: K
authors: Feng
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Meixia
authors: M
authors: Chen
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Yajing
authors: Y
authors: Zhang
authors: Department of Immunology, Institute of Basic Medicine, Medical College of PLA, Chinese PLA General Hospital, Beijing 100853, China.
authors: Yao
authors: Y
authors: Wang
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Fengxia
authors: F
authors: Shi
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Xiaobing
authors: X
authors: Fu
authors: Department of Geriatric Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: Hongli
authors: H
authors: Zhu
authors: Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China ; Department of Immunology, Institute of Basic Medicine, Medical College of PLA, Chinese PLA General Hospital, Beijing 100853, China.
authors: Weidong
authors: W
authors: Han
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002277:Carcinoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods*; D003520:Cyclophosphamide; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004311:Double-Blind Method; D004317:Doxorubicin; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation; D008223:Lymphoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011241:Prednisone; D011446:Prospective Studies; D016019:Survival Analysis; D014750:Vincristine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014750:Vincristine; D000077209:Decitabine; D004317:Doxorubicin; D003520:Cyclophosphamide; D015254:DNA Modification Methylases; D001374:Azacitidine; D011241:Prednisone