Randomized Study of Autologous Cytokine-Induced Killer Cell Immunotherapy in Metastatic Renal Carcinoma

Purpose: 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.Experimental Design: 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-alpha-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.Results: 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. Conclusion: 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. Clin Cancer Res; 18(6); 1751-9. (C) 2012 AACR.

目的：细胞因子诱导的杀伤细胞（CIK）在肾细胞癌（RCC）中的治疗益处尚不明确。本前瞻性随机研究旨在评估自体CIK细胞免疫疗法对转移性透明细胞肾细胞癌患者的疗效。 实验设计：2005年6月至2008年6月，148例转移性透明细胞肾细胞癌患者被随机分为自体CIK细胞免疫疗法组（第1组，n = 74），或白细胞介素 - 2联合干扰素 -α - 2a治疗组（第2组，n = 74）。主要终点是总生存期（OS），次要终点是无进展生存期（PFS），通过卡普兰 - 迈耶分析以及考克斯比例风险模型评估治疗风险比。 结果：第1组的3年无进展生存期和总生存期分别为18%和61%，而第2组分别为12%和23%（分别为P = 0.031和<0.001）。第1组的中位无进展生存期和总生存期明显长于第2组（无进展生存期，12个月对8个月，P = 0.024；总生存期，46个月对19个月，P < 0.001）。多变量分析表明，作为连续变量的CIK细胞免疫疗法的周期数与第1组的无进展生存期延长[风险比 = 0.88；95%置信区间（CI），0.84 - 0.93；P < 0.001]和总生存期（风险比 = 0.58；95%CI，0.48 - 0.69；P < 0.001）显著相关。 结论：数据表明CIK细胞免疫疗法可改善转移性透明细胞肾细胞癌的预后，增加CIK细胞治疗周期数可进一步增强有益效果。《临床癌症研究》；18(6)；1751 - 9。（C）2012美国癌症研究协会。