重组人血管内皮抑制素持续泵入对晚期非小细胞肺癌疗效及血管生成素 2的影响

Effects of continuous infusion of recombinant human endostatin on the treatment of advanced non small cell lung cancer and angiogenin 2

目的探讨重组人血管内皮抑制素联合化疗在晚期非小细胞肺癌(NSCLC)中的有效性、完全性,并探讨血管生成素 2(Ang 2)在预测重组人血管内皮抑制素治疗后肿瘤血管正常化时间窗中的价值。方法选取2015年3月至2016年11月芜湖市第二人民医院收治的ⅢB~Ⅳ期NSCLC病人61例,按照随机数字表法分为两组,对照组(单纯化疗组)32例,观察组(重组人血管内皮抑制素联合化疗组)29例。重组人血管内皮抑制素采用持续静脉泵入的方式,21 d为1周期。每2个周期评价疗效,每周期记录不良反应。所有病人均完成至少2个周期的治疗。采用疾病控制率(DCR)来评估重组人血管内皮抑制素的近期疗效。分别检测重组人血管内皮抑制素给药后第0、2、4、6、8、10、14天血清中Ang 2的浓度。结果在第4周期后,两组间的DCR分别40.0%和76.2%(P<0.05)。治疗过程中与重组人血管内皮抑制素相关的主要毒副反应为窦性心动过速、高血压,未出现出血等严重毒副反应。对照组第0天Ang 2水平为(1216.2±136.8)pg/mL,第2、4、6、8、10、14天分别为(1203.2±136.6)、(1201.0±139.3)、(1156.4±159.1)、(1051.1±132.4)、(1009.8±151.0)、(991.2±128.5)pg/mL,呈缓慢下降。观察组第0天Ang 2水平为(1209.8±104.5)pg/mL,在泵入重组人血管内皮抑制素第2天(1116.5±160.8)pg/mL始有下降趋势,第4天时(832.7±95.2)pg/mL两组间差异有统计学意义,在第8天(407.6±91.1)pg/mL进入平台期,并在随后一段时间第10、14天(360.5±122.2)、(379.4±101.8)pg/mL仍维持在较低的水平,但有逐渐升高趋势。结论重组人血管内皮抑制素静脉泵入联合化疗治疗晚期非小细胞肺癌的近期疗效较单纯化疗好,不良反应无明显增加。重组人血管内皮抑制素可以降低Ang 2浓度,根据Ang 2浓度变化情况来推测重组人血管内皮抑制素治疗后血管正常化血管窗大约在用药后4 d左右开始。Ang 2有可能成为监测重组人血管内皮抑制素治疗后血管正常化时间窗有用的生物标志物。

Objective To investigate the efficacy and completeness of recombinant human endostatin combined with chemotherapy in advanced non small cell lung cancer(NSCLC),in advanced non small cell lung cancer(NSCLC),and to explore the value of angiopoietin 2(Ang 2)in predicting the time window for tumor vascular normalization after recombinant human endostatin treat ment.Methods Sixty onepatients with stageⅢB~ⅣNSCLC admitted to the Second People’s Hospital of Wuhu from March 2015 to November 2016 were selected and divided into two groups according to random number table method,with 32 patients in the control group treated with chemotherapy alone and 29 patients in Endostar group treated with Endostar plus chemotherapy.Re combinant human endostatin was continuously pumped intravenously,with 21 days as a cycle..All patients received at least 2cycles of treatment.Efficacy was evaluated every 2cycles,and adverse reactions were recorded every 1 cycle.Disease control rate(DCR)was used to evaluate the short term efficacy of recombinant human endostatin.Ang 2 in serumwas measured by ELISA on days 2,4,6,8,10,and 14 after Endostartreatment,respectively.Results After four cycles,the value of DCR was 40.0%in control group and 76.2%in Endostargroup,respectively(P<0.05).The main adverse reactions associated with recombinant human endostatin in the course of treatment were sinus tachycardia and hypertension,and no serious adverse reactions such as bleeding were observed.The level of Ang 2 in control group at day 0 was(1216.2±136.8)pg/mL,and at days 2,4,6,8,10,and 14 were(1203.2±136.6),(1201.0±139.3),(1156.4±159.1),(1051.1±132.4),(1009.8±151.0),(991.2±128.5)pg/mL,respectively.The level of Ang 2 in Endostar group on the 0th day was(1209.8±104.5)pg/mL,decreased significantly on day 4,the lowest level appeared from day 8 to day 10 and remained at a low level.The level of Ang 2 in control group decreased slowly.From day4,there was a significant differ ence between the two groups.Conclusion The short term efficacy of recombinant human endostatin intravenous infusion combined with chemotherapy in the treatment of advanced non small cell lung cancer is better than that of chemotherapy alone.Recombinant human endostatin can reduce the concentration of Ang 2,and it is speculated that vascular normalization after treatment with recom binant human endostatin begins about 4 days after treatment.Ang 2 may be a useful biomarker to monitor the time window for vas cular normalization after recombinant human endostatin therapy.