Granulocyte-macrophage colony-stimulating factor improves immunological parameters in patients with refractory solid tumours receiving second-line chemotherapy: Correlation with clinical responses
Granulocyte-macrophage colony-stimulating factor improves immunological parameters in patients with refractory solid tumours receiving second-line chemotherapy: Correlation with clinical responses
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DOI：
10.1016/s0959-8049(97)00053-1
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发表时间：
1997-07-01
影响因子：
8.4
通讯作者：
Papamichail, M
中科院分区：
文献类型：
--
作者：
Baxevanis, CN;Tsavaris, NB;Papamichail, M
在这份报告中，我们研究了接受二线化疗的难治性实体瘤患者皮下注射粒细胞-巨噬细胞集落刺激因子（GM-CSF）的免疫功能。这些患者在体内和体外表现出异常的免疫应答，因此，研究GM-CSF诱导的免疫调节对临床应答的影响是有意义的。我们检查了原发性恶性肿瘤患者，（头颈部10例，泌尿生殖道17例，阴茎6例，结直肠，n = 8），第1天和第22天接受卡铂（JM 8）300 ng/m2，第8天接受甲酰四氢叶酸（LV）200 mg/m2 + 5-氟尿嘧啶（5-FU）500 mg/m2，15和29日注射安慰剂或GM-CSF，300 μ g/天，在第3-6、10-13、17-20和24-27天注射4个周期。在安慰剂或GM-CSF的四个周期注射的每一个结束后一天，即在第7、14、21和28天，从患者收集外周血。外周血单个核细胞（PBMC）在自体混合淋巴细胞反应（AMLR）和自然杀伤（NK）或淋巴因子激活的杀伤（LAK）细胞活性进行了测试。血清中细胞因子水平通过免疫酶联免疫吸附试验（ELISA）测定。共有21例患者接受了四个周期的方案与GM-CSF（组1）和20名类似的治疗与安慰剂（组2）。所有患者均接受上述标准化疗。在GM-CSF治疗前，所有患者均表现出血清白细胞介素-1（IL-1 β）、肿瘤坏死因子-α（TNF-α）、IL-6和前列腺素E-2（PGE（2））水平升高，血清IL-2水平降低。所有患者的细胞免疫反应（AMLR，NK和LAK细胞毒性）也较低。第1组5例患者PR（部分缓解），2例患者CR（完全缓解），14例患者病情稳定。第2组7例患者显示疾病进展，3例患者PR，10例患者疾病稳定。治疗期间，第1组的所有免疫参数均显著改善，但第2组保持不变甚至恶化。在用常规化疗药物治疗癌症患者期间施用GM-CSF导致体外缺陷细胞免疫应答的显著增强和细胞因子血清水平向正常化的变化。本文报道的结果支持在化疗期间使用GM-CSF作为免疫增强剂，但在得出明确的结论之前必须对更多的患者进行研究。(C)1997年由Elsevier Science Ltd.出版
In this report, we studied the immunorestorative properties of subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with refractory solid tumours receiving second-line chemotherapy. Such patients exhibit abnormal immune responses in vivo and in vitro and, therefore, it was of interest to examine the effect of GM-CSF-induced immunomodulation on clinical response. We examined patients with primary malignant carcinomas (head and neck, n = 10; urogenital tract, n = 17; penis n = 6; colorectal, n = 8) who were treated with carboplatin (JM8), 300 ng/m(2) on days 1 and 22, leucovorin (LV), 200 mg/m(2) plus 5-fluoracil (5-FU), 500 mg/m(2) on days 8, 15 and 29 and four cycles of daily injections with placebo or GM-CSF, 300 mu g/day on days 3-6, 10-13, 17-20 and 24-27. Peripheral blood was collected from the patients one day after the end of each of the four-cycle injections with placebo or GM-CSF, namely on days 7, 14, 21 and 28. Peripheral blood mononuclear cells (PBMC) were tested in the autologous mixed lymphocyte reaction (AMLR) and for natural killer (NK) or lymphokine-activated killer (LAK) cell activity. Cytokine levels in serum were measured by immunoenzymatic (ELISA) assay. A total of 21 patients received a four-cycle regimen with GM-CSF (Group 1) and 20 were similarly treated with placebo (Group 2). All received standard chemotherapy as outlined above. Before GM-CSF treatment, all patients exhibited increased serum levels of interleukin-1 (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and prostaglandin E-2 (PGE(2)) and decreased serum levels of IL-2. Cellular immune responses (AMLR, NK- and LAK-cytotoxicity) were also low in all patients. Five patients from Group 1 had a PR (partial response), 2 patients had CR (complete response), and 14 patients had stable disease. Seven patients from Group 2 showed progressive disease, 3 had a PR and 10 had stable disease. All immune parameters were significantly improved during treatment in Group 1 but remained unchanged or even deteriorated in Group 2. Administration of GM-CSF during treatment of cancer patients with conventional chemotherapeutic drugs results in a marked potentiation of deficient cellular immune responses in vitro and a change towards normalisation of cytokine serum levels. The results reported herein support the use of GM-CSF as immunopotentiator during chemotherapy, but more patients must be studied before definite conclusions can be drawn. (C) 1997 Published by Elsevier Science Ltd.