Ullenhag Gustav J, Mozaffari Fariba, Broberg Mats, Mellstedt Håkan, Liljefors Maria
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Department of Oncology, Uppsala University Hospital, Entrance 78, Uppsala, Sweden.
PLoS One. 2017 Jan 18;12(1):e0169736. doi: 10.1371/journal.pone.0169736. eCollection 2017.
To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer.
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.
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.
Patients with advanced pancreatic carcinoma had impaired immune functions. Lenalidomide 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.
ClinicalTrials.gov NCT01547260.
评估来那度胺联合吉西他滨标准治疗方案对晚期胰腺癌患者的免疫调节作用及临床疗效。
晚期胰腺癌患者一线接受来那度胺口服治疗，每28天为一个周期，其中21天服用药物，并联合吉西他滨标准治疗方案。在我们之前报道的第一部分研究中，确定了来那度胺的剂量（n = 12）。在第二部分研究中，第1周期时，每隔一位连续入组的患者接受来那度胺治疗（A组，n = 11）或吉西他滨治疗（B组，n = 10）。从第2周期开始，所有第二部分研究的患者均接受联合治疗。
与健康对照者相比，晚期胰腺癌患者基线时外周血单个核细胞增殖反应及树突状细胞频率显著降低，而患者的CD4⁺和CD8⁺T细胞、自然杀伤细胞及骨髓来源抑制细胞频率显著高于对照者。在A组，治疗期间活化（HLA-DR⁺）CD4和CD8 T细胞及CD8效应记忆T细胞的绝对数量显著增加（p<0.01）。第1周期后调节性T细胞的绝对数量有统计学增加（p<0.05）。加入吉西他滨后，大多数淋巴细胞亚群减少（p<0.05）。在B组，研究期间淋巴细胞比例保持不变。两组在总生存期、无进展生存期及1年生存率方面无差异。
晚期胰腺癌患者免疫功能受损。来那度胺增强T细胞反应性，但被吉西他滨消除。然而，在这项非随机研究中，与单独使用吉西他滨相比，来那度胺联合吉西他滨似乎没有治疗效果。
ClinicalTrials.gov NCT01547260。
