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Clinical and Immune Effects of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, Dept Oncol, Entrance 78, Uppsala, Sweden..
Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden..
Danderyd Hosp, Dept Oncol, Stockholm, Sweden..
Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden..
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0169736Article in journal (Refereed) Published
Abstract [en]

Purpose To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer. Patients and Methods Patients with advanced pancreatic cancer were treated in first line with lenalidomide orally for 21 days of a 28 days cycle and the standard regimen for gemcitabine. In Part I, which we previously have reported, the dose of lenalidomide was defined (n = 12). In Part II, every other consecutive patient was treated with either lenalidomide (Group A, n = 11) or gemcitabine (Group B, n = 10) during cycle 1. From cycle 2 on, all Part II patients received the combination. Results A significant decrease in the proliferative response of peripheral blood mononuclear cells and the frequency of DCs were noted in patients at baseline compared to healthy control donors while the frequencies of CD4+ and CD8+ T cells, NK-cells and MDSCs were significantly higher in patients compared to controls. In Group A, a significant increase in the absolute numbers of activated (HLA-DR+) CD4 and CD8 T cells and CD8 effector memory T cells (p<0.01) was noted during treatment. A statistical increment in the absolute numbers of Tregs were seen after cycle 1 (p<0.05). The addition of gemcitabine, reduced most lymphocyte subsets (p<0.05). In Group B, the proportion of lymphocytes remained unchanged during the study period. There was no difference in overall survival, progression free survival and survival rate at one year comparing the two groups. Discussion Patients with advanced pancreatic carcinoma had impaired immune functions. Lenalido-mide augmented T cell reactivities, which were abrogated by gemcitabine. However, addition of lenalidomide to gemcitabine seemed to have no therapeutic impact compared to gemcitabine alone in this non-randomized study.

Place, publisher, year, edition, pages
2017. Vol. 12, no 1, article id e0169736
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Cancer and Oncology
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URN: urn:nbn:se:uu:diva-316028DOI: 10.1371/journal.pone.0169736ISI: 000392380100031PubMedID: 28099502OAI: oai:DiVA.org:uu-316028DiVA, id: diva2:1076910
Funder
Swedish Cancer Society, 110711The Karolinska Institutet's Research FoundationStockholm County Council
Available from: 2017-02-24 Created: 2017-02-24 Last updated: 2017-11-29Bibliographically approved

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