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Journal of Immunology Research
Volume 2014, Article ID 371087, 14 pages
http://dx.doi.org/10.1155/2014/371087
Clinical Study

Low-Dose Decitabine-Based Chemoimmunotherapy for Patients with Refractory Advanced Solid Tumors: A Phase I/II Report

1Department of Bio-Therapy, College of Life Sciences, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
2Department of Geriatric Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
3Department of Immunology, Institute of Basic Medicine, Medical College of PLA, Chinese PLA General Hospital, Beijing 100853, China

Received 26 December 2013; Revised 21 March 2014; Accepted 10 April 2014; Published 21 May 2014

Academic Editor: Shigeo Koido

Copyright © 2014 Hui Fan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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).