自体CIK细胞联合卡培他滨维持治疗复发转移性三阴性乳腺癌效果观察

Clinical Efficacy of Capecitabine Combined with Autologous Cytokine-induced Killer Cells Maintenance Therapy in Treatment of Metastatic Triple Negative Breast Cancer

目的探讨自体细胞因子诱导杀伤细胞(CIK)免疫治疗联合卡培他滨治疗复发转移性三阴性乳腺癌(metastatic triple negative breast cancer,MTNBC)的临床效果和安全性。方法选取一线应用卡培他滨化疗后效果评价病情稳定(SD)或以上的MTNBC患者,随机分为治疗组和对照组。两组均应用卡培他滨维持化疗,治疗组在此基础上予CIK细胞免疫治疗。一线化疗末次周期结束后15 d进行基线评估,治疗期间随化疗周期进行随访,出院后每2周期随访1次,中位随访时间11.2个月。观察两组外周血T细胞亚群变化、不良反应及无进展生存期(PFS)、总生存期(OS)并进行比较。结果治疗组CD3+CD8+CTL细胞、CD4+CD25+Treg细胞在一线化疗后基线评估时和CIK第3周期治疗后1个月对比,差异无统计学意义(P>0.05),CD3+T细胞、CD3+CD4+Th细胞、CD3+CD56+CIK细胞则较治疗前显著升高(P<0.05)。发热治疗组8例(18.2%),对照组2例(4.5%),组间比较差异有统计学意义(P<0.05),余不良反应(手足综合征、药物性肝损害、胃肠道反应、骨髓抑制等)无明显差异。治疗组与对照组的1年无进展生存率分别为18.2%和9.1%,差异有统计学意义(P<0.05);OS(均为16.5个月)则无明显差异(P>0.05)。结论 CIK细胞联合卡培他滨治疗MTNBC,可改善患者的免疫功能,延长PFS,提高MTNBC维持治疗的近期效果,具有良好的安全性。

Objective To analyze the clinical efficacy and safety of capecitabine combined with autologous cytokineinduced killer cells（ CIK） maintenance therapy in treatment of metastatic triple negative breast cancer（ MTNBC）. Methods The MTNBC patients undergoing capecitabine-based chemotherapy as first line treatment,whose therapeutic effect was SD or above were selected and divided into treatment group and control group randomly. The treatment group received capecitabine maintenance therapy with autologous CIK after the first line treatment. The control group underwent only capecitabine maintenance therapy. Baseline assessment was taken 15 d after the end of the last cycle of chemotherapy. The patients were followed up once every two cycles. The median follow-up time was 11. 2 months. T lymphocyte subpopulation in peripheral blood was measured,the side effects,PFS and OS of both groups were observed. Results CD3 ＋ CD8 ＋ CTL and CD4 ＋ CD25 ＋ Treg of treatment group were compared at the time of baseline assessment and 1 month after three cycles of chemotherapy. There was no statistically significant difference（ P〈0. 05）. CD3 ＋ T,CD3 ＋ CD4 ＋ Th,CD3 ＋ CD56 ＋ CIK showed significant improvement,compared with that before treatment（ P〈0. 05）. The adverse reaction showed that in the treatment group there were 8 patients with fever（ 18. 2%）,and 2 patients in control group（ 4. 5%）. The difference was statistically significant（ P〈0. 05）. The rest（ extremities syndrome,drug-induced liver damage,bone marrow suppression and gastrointestinal reaction,etc） showed no significant difference. The PFS rate of one year in the two groups was 18. 2% and 9. 1% respectively.The difference was statistically significant（ P〈0. 05）. OS of the two groups was 16. 5 months with no statistically significant difference（ P〈0. 05）. Conclusion Maintenance therapy of Capecitabine combined with autologous CIK cells in treatment of MTNBC after first-line treatment improves the immune function to enhance the ability of antitumor by natural immunity,which can prolong PFS,and is safe as well. In short,it can improve the therapeutic effect of maintenance therapy in patients with MTNBC.