CIK治疗转移性肾癌的临床疗效评价及预后影响因素分析

Clinical Efficacy and Related Predictive Factors of Cytokine-induced Killer Cells in the Treatment of Patients with Metastatic Renal Cell Carcinoma

目的:评价细胞因子诱导的杀伤细胞(cytokine-induced killer cells,CIK)免疫治疗在晚期转移性肾癌(metastatic renalcell carcinoma,MRCC)治疗中的作用。方法:连续收集天津医科大学附属肿瘤医院2002年3月至2010年7月接受CIK细胞治疗的80例MRCC患者为治疗组,88例接受IL-2联合IFN治疗的MRCC患者为对照组。配对因素包括性别、年龄、KPS评分、中性粒细胞计数、血小板、血红蛋白、乳酸脱氢酶、β2-微球蛋白、血钙、确诊至开始内科治疗的时间、转移部位数量等。观察终点为无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。结果:CIK治疗组患者1、2、3年无进展生存率分别为47%、28%、17%,而对照组患者分别为36%、15%、10%(P值分别为0.015、0.009、0.019)。CIK治疗组患者1、2、3年总生存率分别为87%、67%、59%,而对照组患者分别为55%、37%、18%(P均<0.001)。CIK治疗组患者的中位PFS、OS明显优于对照组(12个月vs.9个月,P=0.013:46个月vs.18个月,P<0.001)。多因素分析显示,KPS评分、转移部位数量、CIK细胞治疗的次数与CIK治疗组患者预后具有明显相关性。最佳CIK治疗次数为7次以上。结论:CIK细胞免疫治疗可以显著改善MRCC患者预后。高KPS评分、无或仅有一个转移部位的患者预后较好,且增加CIK免疫治疗次数可以使患者更大程度获益。

Objective： To evaluate the clinical efficacy and analyze the related predictive factors of cytokine-induced killer cells （ CIK ） in the treatment of patients with metastatic renal cell carcinoma （ MRCC ）. Methods： Baseline characteristics and outcomes of 168 patients with MRCC were collected from the Tianjin Medical University Cancer Institute and Hospital from March 2002 to July 2010. A total of 80 patients received autologous CIK cell treatment （ CIK group ）, and 88 received IL-2 treatment combined with IFN-α （ control group ）. Progression-free survival （PFS） and overall survival （ OS ） were evaluated. Results： The 1-, 2-, and 3-year PFS rates in the CIK group were 47 %, 28 %, and 17 %, compared with the 36%, 15% and 10% in the control group （ P = 0.015, 0.009, and 0.019, respectively ）. The 1-, 2-, and 3-year OS rates in the CIK group were 87%, 67%, and 59%, compared with 55%, 37%, and 18% in the control group （ P 〈 0.001 for all ）. The median PFS and OS durations in the CIK group were significantly higher than those in the control group （ 12 months vs. 9 months, P - 0.013; and 46 months vs. 18 months, P 〈 0.001, respectively ）. Multivariate analysis re- vealed that the Karnofsky performance status （KPS）, number of metastatic sites, and frequency of CIK cell immunotherapy were signifi- cantly related with the OS duration. The optimal cutpoint of frequency was seven times. Conclusion： The data suggested for the first time that CIK cell immunotherapy can improve the prognosis of MRCC. Patients with higher KPS and no more than one metastatic site have a better survival rate. Increasing the frequency of CIK cell treatment seems to benefit patients more.