Immunity feedback and clinical outcome in colon cancer patients undergoing chemoimmunotherapy with gemcitabine plus FOLFOX followed by subcutaneous granulocyte macrophage colony-stimulating factor and aldesleukin (GOLFIG-1 trial)
Immunity feedback and clinical outcome in colon cancer patients undergoing chemoimmunotherapy with gemcitabine plus FOLFOX followed by subcutaneous granulocyte macrophage colony-stimulating factor and aldesleukin (GOLFIG-1 trial)
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DOI：
10.1158/1078-0432.ccr-07-5278
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发表时间：
2008-07-01
影响因子：
11.5
通讯作者：
Francini, Guido
中科院分区：
文献类型：
--
作者：
Correale, Pierpaolo;Tagliaferri, Pierosandro;Francini, Guido
目的：GOLFIG化学免疫治疗方案被证明是晚期结肠癌患者安全且非常有效的化学免疫治疗方案。因此，我们研究了治疗的免疫生物学反馈及其与这些患者临床结果的可能相关性。 实验设计：这项临床和免疫学研究涉及 46 名患者，其中 27 名男性和 19 名女性，参加了 GOLFIG-1 II 期试验，他们接受吉西他滨（第 1 天和第 15 天为 1,000 mg/m(2)）、奥沙利铂（第 2 天为 85 mg/m(2)， 16)、左亚叶酸（第 1、2、15 和 16 天 100 mg/m(2)）和 5-氟尿嘧啶（400 mg/m(2) 推注，第 1、2、15 和 16 天 24 小时输注 800 mg/m2），然后皮下注射。粒细胞巨噬细胞集落刺激因子（100 μg，第 3-7 天）和白细胞介素 2（0.5 x 10(6) IU，每天两次，第 8-14 和 17-29 天）。 结果：该方案被证实对于已接受治疗的转移性结直肠癌患者是安全且非常有效的。对这些患者的亚组分析显示，六名出现自身免疫晚期症状的患者的进展时间和生存期延长。多变量分析验证了自身免疫体征的发生是良好结果的独立预测因素。一项平行免疫学研究在这些患者的外周血单核细胞中检测到淋巴细胞和嗜酸性粒细胞计数逐渐增加、中枢记忆增强、免疫抑制性调节性 T 细胞显着减少以及结肠癌特异性细胞毒性 T 细胞的激活。 结论：我们的结果表明，GOLFIG 方案的免疫反馈与其抗肿瘤活性密切相关。
Purpose: GOLFIG chemoimmunotherapy regimen proved to be a safe and very active chemoimmunotherapy regimen in advanced colon cancer patients. We have thus investigated the immunobiological feedback to the treatment and its possible correlation with the clinical outcome of these patients.Experimental Design:This clinical and immunologic study involved 46 patients, 27 males and 19 females, enrolled in the GOLFIG-1 phase II trial who received gemcitabine (1,000 mg/m(2) on days 1 and 15), oxaliplatin (85 mg/m(2) on days 2 and 16), levofolinic acid (100 mg/m(2) on days 1, 2, 15, and 16), and 5-fluorouracil (400 mg/m(2) as a bolus, and 800 mg/m2 as a 24-hour infusion on days 1, 2, 15, and 16) followed by s.c. granulocyte macrophage colony-stimulating factor (100 mu g, on days 3-7) and interleukin 2 (0.5 x 10(6) IU twice a day on days 8-14 and 17-29).Results: The regimen was confirmed to be safe and very active in pretreated patients with metastatic colorectal cancer. A subgroup analysis of these patients revealed a prolonged time to progression and survival in six patients who developed late signs of autoimmunity. A multivariate analysis validated the occurrence of autoimmunity signs as an independent predictor of favorable outcome. A parallel immunologic study detected in the peripheral blood mononuclear cells of these patients a progressive increase in lymphocyte and eosinophil counts, amplification in central memory, a marked depletion of immunosuppressive regulatory T cells, and activation of colon cancer-specific cytotoxic T cells.Conclusions: Our results suggest that immunity feedback to GOLFIG regimen and its antitumor activity are tightly correlated.