腹腔灌注贝伐珠单抗联合紫杉醇和铂类化疗对Ⅲb~Ⅳ期卵巢癌患者血清肝细胞生长因子和巨噬细胞移动抑制因子水平的影响

Effect of intraperitoneal perfusion of bevacizumab combined with paclitaxel and platinum chemotherapy on serum hepatocyte growth factor and macrophage migration inhibitory factor in patients with stage Ⅲb-Ⅳ ovarian cancer

目的 分析腹腔灌注贝伐珠单抗联合紫杉醇和铂类化疗对Ⅲb~Ⅳ期卵巢癌患者血清肝细胞生长因子(HGF)和巨噬细胞移动抑制因子(MIF)水平的影响,为卵巢癌患者的治疗提供参考依据。方法 选取2019年1—12月浙江衢化医院收治的80例Ⅲb~Ⅳ期卵巢癌患者,采用随机数字表分为观察组和对照组,每组40例患者。两组均行卵巢肿瘤细胞减灭手术,对照组术后采用紫杉醇、顺铂静脉化疗,观察组在对照组基础上增加贝伐珠单抗腹腔灌注。比较两组临床疗效和毒副反应,治疗前和治疗9周后评估两组血清肿瘤标志物水平[癌抗原125(CA125)、MIF及人附睾蛋白4(HE4)]、肿瘤细胞因子[HGF、血管内皮生长因子(VEGF)及碱性成纤维因子(bFGF)]及免疫功能指标(CD3^(+)T淋巴细胞亚群、CD4^(+)T淋巴细胞亚群、CD4^(+)/CD8^(+)T淋巴细胞亚群比值),随访患者1年生存率。结果 80例患者均完成治疗。观察组治疗总有效率(77.50%)显著高于对照组(52.50%),差异有统计学意义(χ^(2)=5.495,P=0.019)。观察组骨髓抑制、恶心呕吐、腹泻、肝损害及肾损害发生率(0~Ⅰ度:67.50%、80.00%、80.00%、95.00%、97.50%;Ⅱ~Ⅳ度:32.50%、20.00%、20.00%、5.00%、2.50%)与对照组(0~Ⅰ度:72.50%、87.50%、90.00%、97.50%、100.00%;Ⅱ~Ⅳ度:27.50%、12.50%、10.00%、2.50%、0.00%)比较,差异均无统计学意义(χ^(2)=0.238,0.827,1.569,0.346,0.000,均P>0.05)。治疗9周后,两组血清CA125、MIF、HE4、HGF、VEGF及bFGF水平均低于治疗前[观察组:(92.95±11.09)U/ml、(14.84±3.15)ng/ml、(645.89±62.26)pmol/L、(12.36±1.60)ng/ml、(59.71±9.06)ng/ml、(121.58±29.72)ng/L;对照组:(94.20±10.29)U/ml、(14.77±3.70)ng/ml、(639.67±69.92)pmol/L、(12.98±1.68)ng/ml、(57.83±11.28)ng/ml、(124.58±27.15)ng/L],差异均有统计学意义(均P<0.05),观察组治疗后血清CA125、MIF、HE4、HGF、VEGF及bFGF水平[(27.62±7.52)U/ml、(4.34±1.70)ng/ml、(232.33±45.06)pmol/L、(6.35±1.24)ng/ml、(21.84±5.55)ng/ml、(74.19±18.03)ng/L]均低于同期对照组[(42.98±6.35)U/ml、(7.59±2.54)ng/ml、(410.26±47.57)pmol/L、(9.43±1.99)ng/ml、(30.57±5.84)ng/ml、(94.19±15.08)ng/L],差异均有统计学意义(均P<0.05)。治疗9周后,观察组CD3^(+)T淋巴细胞亚群、CD4^(+)T淋巴细胞亚群[(28.47±3.35)%、(26.02±4.06)%]与对照组[(27.88±3.20)%、(26.77±5.95)%]均低于治疗前[观察组:(31.94±3.76)%、(32.22±5.06)%;对照组:(31.92±3.42)%、(32.45±5.61)%](均P<0.05),两组治疗前后CD4^(+)/CD8^(+)T淋巴细胞亚群比值[观察组:(1.17±0.52)、(1.07±0.29);对照组:(1.18±0.58)、(1.05±0.28)]比较差异均无统计学意义(均P>0.05)。观察组1年生存率(82.50%)显著高于对照组(60.00%),差异有统计学意义(χ^(2)=4.943,P=0.026)。结论 腹腔灌注贝伐珠单抗联合紫杉醇和铂类化疗可有效降低晚期卵巢癌患者血清肿瘤标志物和相关肿瘤细胞因子水平,能通过多种增效作用改善患者临床疗效和预后,安全性较好。

Objective To analyze the effect of intraperitoneal perfusion of bevacizumab combined with paclitaxel and platinum chemotherapy on serum hepatocyte growth factor(HGF) and macrophage migration inhibition factor(MIF) in patients with stage Ⅲb-Ⅳ ovarian cancer, provide a reference basis for treatment of ovarian cancer.Methods From January to December in 2019, 80 patients with stage Ⅲb-Ⅳ ovarian cancer were selected from Zhejiang Quhua Hospital and divided into observation group and control group according to random number table, 40 cases in each group. The patients in the two groups underwent ovarian tumor cytoreductive surgery, the patients in control group underwent intravenous chemotherapy combined with paclitaxel and cisplatin after operation, while the patients in observation group underwent intraperitoneal perfusion of bevacizumab on the basis of intravenous chemotherapy with paclitaxel and cisplatin after operation.The clinical effects and toxic and adverse effects in the two groups were compared.Before treatment and at nine weeks after treatment, the levels of serum tumor markers [cancer antigen 125(CA125), MIF, and human epididymal protein 4(HE4)], tumor cytokines [HGF, vascular endothelial growth factor(VEGF), and basic fibroblast factor(bFGF)], and immune function indexes(CD3T lymphocyte subgroup, CD4T lymphocyte subgroup, and CD4/CD8T lymphocyte subgroup ratio).The one-year survival rates of patients in the two groups were followed up.Results Treatment was completed in the 80 patients.The total effective rate in observation group(77.50%) was statistically significantly higher than that in control group(52.50%)(χ^(2)=5.495, P=0.019).There was no statistically significant difference in the incidence rates of bone marrow suppression, nausea and vomiting, diarrhea, liver damage and kidney damage between observation group(degree 0-Ⅰ: 67.50%, 80.00%, 80.00%, 95.00%, 97.50%;degree Ⅱ-Ⅳ: 32.50%, 20.00%, 20.00%, 5.00%, 2.50%) and control group(degree 0-Ⅰ: 72.50%, 87.50%, 90.00%, 97.50%, 100.00%;degree Ⅱ-Ⅳ: 27.50%, 12.50%, 10.00%, 2.50%, 0.00%)(χ^(2)=0.238, 0.827, 1.569, 0.346, 0.000, P>0.05).After 9 weeks of treatment, the levels of CA125, MIF, HE4, HGF, VEGF, and bFGF in the two groups were statistically significantly lower than those before treatment [observation group:(92.95±11.09) U/ml,(14.84±3.15) ng/ml,(645.89±62.26) pmol/L,(12.36±1.60) ng/ml,(59.71±9.06) ng/ml,(121.58±29.72) ng/L;control group:(94.20±10.29) U/ml,(14.77±3.70) ng/ml,(639.67±69.92) pmol/L,(12.98±1.68) ng/ml,(57.83±11.28) ng/ml,(124.58±27.15) ng/L](P<0.05);the levels of CA125, MIF, HE4, HGF, VEGF, and bFGF in observation group after treatment [(27.62±7.52) U/ml,(4.34±1.70) ng/ml,(232.33±45.06) pmol/L,(6.35±1.24) ng/ml,(21.84±5.55) ng/ml,(74.19±18.03)ng/L] were statistically significantly lower than those in control group [(42.98±6.35) U/ml,(7.59±2.54) ng/ml,(410.26±47.57) pmol/L,(9.43±1.99) ng/ml,(30.57±5.84) ng/ml,(94.19±15.08) ng/L](P<0.05).After nine weeks of treatment, the levels of CD3T lymphocyte subgroup and CD4T lymphocyte subgroup in observation group [(28.47±3.35)%,(26.02±4.06)%] and control group [(27.88±3.20)%,(26.77±5.95)%] were statistically significantly lower than those before treatment [observation group:(31.94±3.76)%,(32.22±5.06)%;control group:(31.92±3.42)%,(32.45±5.61)%](P<0.05);there was no statistically significant difference in CD4/CD8T lymphocyte subgroup ratio between before and after treatment in the two groups [observation group:(1.17±0.52),(1.07±0.29);control group:(1.18±0.58),(1.05±0.28)](P>0.05).One-year survival rate in observation group(82.50%) was statistically significantly higher than that in control group(60.00%)(χ^(2)=4.943, P=0.026).Conclusion Intraperitoneal perfusion of bevacizumab combined with paclitaxel and platinum chemotherapy can effectively reduce the levels of serum tumor markers and related tumor cytokines, which can improve clinical efficacy and prognosis of patients through many synergistic effect, the safety is relatively good.