Phase Ib/II study of safety and efficacy of low-dose decitabine-primed chemoimmunotherapy in patients with drug-resistant relapsed/refractory alimentary tract cancer

Meixia Chen, Jing Nie, Yang Liu, Xiang Li, Yan Zhang, Malcolm V. Brock, Kaichao Feng, Zhiqiang Wu, Xiaolei Li, Lu Shi, Suxia Li, Mingzhou Guo, Qian Mei, Weidong Han

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1530-1540
Number of pages11
JournalInternational Journal of Cancer
Volume143
Issue number6
DOIs
StatePublished - Sep 15 2018

Keywords

  • alimentary tract cancer
  • chemoimmunotherapy
  • drug resistance
  • hypomethylation agent
  • relapsed/refractory

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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