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      Efficacy of cytokine-induced killer cells in the treatment of elderly patients with metastatic pancreatic adenocarcinoma

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          Abstract

          Currently, metastatic pancreatic cancer is associated with disappointing survival outcomes. This is largely due to a rapid progression of the disease and a precipitous deterioration in the health of affected individuals, especially elderly patients who are often unable to tolerate chemotherapy. The aim of this study was to evaluate the efficacy and safety of adoptive immunotherapy using cytokine-induced killer cells (CIK) as a first-line treatment for metastatic pancreatic cancer. Between December 2010 and June 2012 eight patients were enrolled in this study. All participants were elderly, suffering from metastatic pancreatic cancer, and unable to tolerate chemotherapy. All patients in this study received R-CIK therapy only as a first-line treatment. In the eight patients, 1 had complete response (CR), 5 had stable disease (SD) and 2 had progression disease (PD). Therefore, the overall response rate (ORR) was 12.5% (1/8) and the disease control rate (DCR) was 75.0% (6/8 patients). The 1-year survival rate was 37.5%, and the median overall survival time (mOS) was 13.04 months (95% CI: 5.9-20.2). The results indicated that no significant positive or negative predictive factors were identified by univariate analysis. The main adverse effect of R-CIK was fever and the side effect rate was 25.0% (2/8). Adoptive immunotherapy using R-CIK cells showed comparable OS to survival data seen in previous trials assessing conventional chemotherapies in elderly patients and the adverse effect is less pronounced.

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          Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer

          Background Single-agent gemcitabine (GEM) is a standard treatment for advanced and metastatic pancreatic cancer. This study examines the question whether GEM-based combination chemotherapy can further improve treatment efficacy. Methods A meta-analysis was performed to evaluate randomized trials comparing GEM versus GEM+X (X = cytotoxic agent). Fifteen trials including 4465 patients were eligible for an analysis of overall survival, the primary end-point of this investigation. Results The meta-analysis revealed a significant survival benefit for GEM+X with a pooled hazard ratio (HR) of 0.91 (95% CI: 0.85 – 0.97, p = 0.004). The overall test for heterogeneity resulted in p = 0.82 (I2 = 0%). The analysis of platinum-based combinations indicated a HR of 0.85 (95% CI: 0.76 – 0.96, p = 0.010), while for fluoropyrimidine-based combinations the HR was 0.90 (95% CI: 0.81 – 0.99, p = 0.030). No risk reduction was observed in the group of trials combining GEM with irinotecan, exatecan or pemetrexed (HR = 0.99). A meta-analysis of the trials with adequate information on baseline performance status (PS) was performed in five trials with 1682 patients. This analysis indicated that patients with a good PS had a marked survival benefit when receiving combination chemotherapy (HR = 0.76; 95% CI: 0.67 – 0.87; p < 0.0001). By contrast, application of combination chemotherapy to patients with an initially poor PS appeared to be ineffective (HR = 1.08; 95% CI: 0.90 – 1.29, p = 0.40). Conclusion The meta-analysis of randomized trials indicated a significant survival benefit when GEM was either combined with platinum analogs or fluoropyrimidines. Based on a preliminary subgroup analysis (representing 38% of all patients included in this meta-analysis), pancreatic cancer patients with a good PS appear to benefit from GEM-based cytotoxic combinations, whereas patients with a poor PS seem to have no survival benefit from combination chemotherapy.
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            [New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)].

            This paper is an overview of the new response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1), with a focus on updated contents.
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              Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma.

              The therapeutic benefit of the cytokine-induced killer (CIK) cells was unknown in the renal cell carcinoma (RCC). This prospectively randomized study was conducted to evaluate the effects of autologous CIK cell immunotherapy in patients with metastatic clear cell RCCs. From June 2005 to June 2008, 148 patients with metastatic clear cell RCC were randomized to autologous CIK cell immunotherapy (arm 1, n = 74), or interleukin-2 treatment combination with IFN-α-2a (arm 2, n = 74). The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS) evaluated by Kaplan-Meier analyses and treatment HRs with the Cox proportional hazards model. The 3-year PFS and OS in arm 1 were 18% and 61%, as compared with 12% and 23% in arm 2 (P = 0.031 and <0.001, respectively). The median PFS and OS in arm 1 were significantly longer than those in arm 2 (PFS, 12 vs. 8 months, P = 0.024; OS, 46 vs. 19 months, P < 0.001). Multivariate analyses indicated that the cycle count of CIK cell immunotherapy as a continuous variable was significantly associated with prolonged PFS [HR = 0.88; 95% confidence interval (CI), 0.84-0.93; P < 0.001] and OS (HR = 0.58; 95% CI, 0.48-0.69; P < 0.001) in arm 1. The data suggested that CIK cell immunotherapy could improve the prognosis of metastatic clear cell RCC, and increased cycle count of CIK cell treatment could further enhance the beneficial effects.
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                Author and article information

                Journal
                Cent Eur J Immunol
                Cent Eur J Immunol
                CEJI
                Central-European Journal of Immunology
                Polish Society of Experimental and Clinical Immunology
                1426-3912
                1644-4124
                03 August 2015
                2015
                : 40
                : 2
                : 188-193
                Affiliations
                [1 ]Department of Immunotherapy, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
                [2 ]School of Life Sciences, Zhengzhou University, Zhengzhou, China
                [3 ]Weill Cornell Medical College, New York, USA
                [4 ]Department of Research and Foreign Affairs, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
                [5 ]Institute of Cancer Research, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
                Author notes
                Correspondence: Ling Mai, Institute of Cancer Research, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Dong Ming Road Number 127, Jin Shui District, Zhengzhou, 450008, China. phone: 86-0371-65588018, fax: 86-0371-65587307. e-mail: mailing65588018@ 123456163.com

                Wei Li and Yaomei Wang contributed the same work to this study.

                Article
                25456
                10.5114/ceji.2015.52833
                4637394
                10af0180-c1f2-42b7-9679-5eb71fd75434
                Copyright © Central European Journal of Immunology 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 December 2014
                : 10 March 2015
                Categories
                Original Article

                cytokine-induced killer cells,elderly pancreatic adenocarcinoma,immunotherapy

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