重组人血管内皮抑素联合栓塞化疗治疗中晚期原发性肝癌的临床研究

Clinical study on recombinant human endostatin combined with transcatheter arterial chemoembolization in treatment with advanced primary hepatic carcinoma

目的比较重组人血管内皮抑素(rh-ES)联合经导管肝动脉化疗栓塞(TACE)与单纯TACE治疗中晚期原发性肝癌(PHC)的临床疗效。方法中晚期PHC患者85例行TACE治疗,根据TACE前后是否应用rh-ES注射液分为观察组(45例)、对照组(40例),对比2组TACE术后近期疗效、血清标志物[甲胎蛋白(AFP)、胰岛素样生长因子Ⅱ(IGF-Ⅱ)、胰岛素样生长因子结合蛋白-2(TGFBP-2)、血管内皮生长因子(VEGF)]水平及化疗期间药物不良反应,随访观察2组患者生存时间。结果观察组总体有效率为20.0%,临床获益率为88.9%,均高于对照组的12.5%、80.0%,差异均无统计学意义(x^2=0.866、1.292,P>0.05)。与术前比较,2组TACE术后2个月,患者血清AFP、IGF-Ⅱ、IGFBP-2、VEGF水平均明显下降(t_观=20.658、12.453、14.597、21.797,t_对=15.374、7.950、10.968、11.091,P<0.05);观察组治疗后上述指标水平均显著低于对照组,差异有统计学意义(t=2.870、8.123、2.714、6.994,P<0.05)。2组骨髓抑制、胃肠道反应、肝功能损害、发热等常见毒性反应发生率无明显差异(P>0.05),观察组注射rh-ES后心律失常发生率(11.1%)高于对照组(2.5%),差异无统计学意义(P>0.05)。观察组和对照组TACE术后中位生存时间分别为(21.0±1.1)个月、(15.0±1.3)个月,2组生存时间比较差异有统计学意义(x^2=4.227,P=0.040)。观察组TACE术后12个月生存率为80.0%、24个月生存率为42.2%均高于对照组的67.5%、27.5%,但差异均无统计学意义(x^2=1.725,P=0.189;x^2=2.010,P=0.156)。结论 TACE基础上联合应用rh-ES治疗中晚期PHC,能抑制肿瘤血管的生成,提高近期疗效与远期生存时间;rh-ES使用过程中要注意对心血管系统的毒性作用。

Objective To compare the clinical curative effect of recombinant human endostatin （ rh-ES） combined with transcatheter arterial chemoembolization （ TACE） and single TACE in the treatment of advanced primary hepatocellular carcinoma（PHC）.Methods 85 cases of advanced PHC patients underwent TACE treatment.According to whether applied the injection of rh-ES before and after TACE, they were divided into observation group （45 cases）, control group （40 cases）. Two groups’ TACE postoperative curative effect in the near future were compared , serum marker [alpha fetal protein （AFP）, insulin like growth factor II （IGF-II） , insulin like growth factor binding protein 2 （TGFBP-2）, vascular endothelial growth factor （ VEGF） ] and chemotherapy drug adverse reaction were compared between the two groups. All patients were followed up for survival time .Results Observation group ’ s overall efficiency was 20.0%, and clinical benefit rate was 88.9%, which was higher than the 12.5% and 80.0% in the control group, the difference was not statistically significant （χ2 =0.866,χ2 =1.292, P ＆gt;0.05）.Compared with the preoperative, 2 months after TACE operation, serum AFP, IGF-II, IG-FBP 2 and VEGF levels were significantly decreased in both of the two groups （observation group：t =20.658, t =12.453, t=14.597, t =21.797, control group：t =15.374, t =7.950, t =10.968, t =11.091, P 〈0.05）;after treatment, obser-vation group ’ s indexes level were significantly lower than those of the control group , the difference were statistically significant （ t =2.870, t =8.123, t =2.714, t =6.994, P 〈0.05）.Two groups’ bone marrow suppression, gastrointestinal tract reaction, liver function damage, fever and other common toxicity reaction rate had no significant difference （ P〉0.05）, the observation group after injected rh-ES’ s arrhythmia occurred rate was 11.1%, which was higher than that of the control group’s 2.5%, the difference was not statistically significant （ P 〉0.05）.The observation group and the control group after TACE’s median follow-up time was（21.0 ±1.1） months and （15.0 ±1.3） months, the difference in survival time between the two groups has statistical significance （χ2 =4.227, P =0.040）.In the observation group, TACE postoperative 12 months’ survival rate was 80.0%, 24 months’ survival rate was 42.2%, which were higher than those of control group ’ s 67.5%and 27.5%, but the differences were no statistical significance （χ2 =1.725, P =0.189;χ2 =2.010, P =0.156）. Conclusion Transcatheter arterial chemoembolization （ TACE） combined application of rh-ES in the treatment of advanced PHC can inhibit the formation of tumor blood vessels , improve the short-term effects and long-term survival time;toxic effects on the cardiovascular system should be noticed during using rh-ES.