腹腔灌注贝伐珠单抗联合白蛋白紫杉醇和卡铂治疗卵巢癌所致癌性腹腔粘连的临床探讨

国际肿瘤学杂志››2021,Vol. 48››Issue (11): 660-665.doi:10.3760/cma.j.cn371439-20210607-00131

腹腔灌注贝伐珠单抗联合白蛋白紫杉醇和卡铂治疗卵巢癌所致癌性腹腔粘连的临床探讨

郑静¹, 姚胜², 沈文洁³, 孙志佳¹, 赵辉¹, 付艳¹, 高珂¹, 杜楠¹()

¹中国人民解放军总医院第四医学中心肿瘤内科,北京 100048
²中国人民解放军总医院第四医学中心普通外科,北京 100048
³中国人民解放军总医院第四医学中心妇产科,北京 100048

收稿日期:2021-06-07修回日期:2021-10-01出版日期:2021-11-08发布日期:2021-12-14
通讯作者:杜楠 E-mail:dunan304@163.com
基金资助:
北京市科学技术委员会项目(Z171100000417011)

Clinical study of intraperitoneal infusion of bevacizumab combined with albumin paclitaxel and carboplatin in carcinomatous peritoneal adhesion from ovarian cancer

Zheng Jing¹, Yao Sheng², Shen Wenjie³, Sun Zhijia¹, Zhao Hui¹, Fu Yan¹, Gao Ke¹, Du Nan¹()

¹Department of Oncology, Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China
²Department of General Surgery, Fourth Medical Center of Chinese PLA Genera Hospital, Beijing 100048, China
³Department of Obstetrics and Gynecology, Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China

Received:2021-06-07Revised:2021-10-01Online:2021-11-08Published:2021-12-14
Contact:Du Nan E-mail:dunan304@163.com
Supported by:
Beijing Municipal Science and Technology Project(Z171100000417011)

摘要/Abstract

摘要：

目的观察腹腔灌注贝伐珠单抗联合白蛋白紫杉醇和卡铂治疗卵巢癌所致癌性腹腔粘连的临床疗效。方法研究对象为2016年1月至2020年12月在我院治疗的复发上皮性卵巢癌合并癌性腹腔粘连患者,共54例。按照数字随机表法随机分为试验组(n=27)和对照组(n=27)。试验组治疗方案为静脉输注白蛋白紫杉醇+腹腔灌注卡铂和贝伐珠单抗。对照组治疗方案为静脉输注白蛋白紫杉醇+腹腔灌注卡铂。21 d重复,每2个周期评价一次疗效,共治疗6个周期。比较两组患者的疗效及不良反应发生情况。结果试验组恶性不全性肠梗阻缓解有效率高于对照组[85.19%(23/27)vs. 59.26%(16/27)],试验组治疗总有效率高于对照组[74.07%(20/27)vs. 44.44%(12/27)],差异均有统计学意义(χ²=4.523,P=0.033;χ²=4.909,P=0.027)。治疗后试验组、对照组腹腔积液血管内皮生长因子(VEGF)水平均明显低于治疗前[(80.33±1.41)pg/mlvs. (310.45±3.35)pg/ml,t=449.884,P<0.001;(135.68±1.60)pg/mlvs. (310.46±3.09)pg/ml,t=499.281,P<0.001];且试验组治疗后VEGF水平较对照组下降更为显著(t=-134.907,P<0.001)。试验组和对照组患者对治疗的耐受良好,高血压(11.11%vs.3.70%,χ²=0.270,P=0.603)、中性粒细胞减少(14.81% vs.11.11%,χ²<0.001,P>0.999)、周围神经病变(3.70% vs.0,χ²<0.001,P>0.999)、腹泻(7.41% vs.3.70%,χ²<0.001,P>0.999)、恶心(3.70% vs.0,χ²<0.001,P>0.999)、鼻出血(7.41% vs.0,χ²=0.519,P=0.471)、蛋白尿(3.70% vs.0,χ²<0.001,P>0.999)不良反应发生率差异均无统计学意义。结论腹腔灌注贝伐珠单抗联合化疗治疗卵巢癌所致癌性腹腔粘连优于单纯化疗。

关键词:卵巢肿瘤,血管生成抑制剂,腹腔粘连,恶性肠梗阻,贝伐珠单抗

Abstract:

ObjectiveTo observe the clinical effects of intraperitoneal perfusion of bevacizumab combined with albumin paclitaxel and carboplatin in the treatment of malignant peritoneal adhesion caused by ovarian cancer.MethodsFrom January 2016 to December 2020, 54 patients treated in our hospital with malignant peritoneal adhesions caused by ovarian cancer were enrolled in this study. They were randomly divided into experimental group (n=27) and control group (n=27) according to the random number table method. The treatment regimen of the experimental group was intravenous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin and bevacizumab. The treatment regimen of the control group was intra-venous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin. The treatment was repeated every 21 days, and the therapeutic effect was evaluated every two cycles. The treatment lasted for six cycles. The efficacy and incidence of adverse reactions were compared between the two groups.ResultsThe remission rate of incomplete malignant bowel obstruction of the experimental group was higher than that of the control group [85.19% (23/27)vs. 59.26% (16/27)], the total effective rate of the experimental group was higher than that of the control group [74.07% (20/27)vs. 44.44% (12/27)], and there were statistically significant differences (χ²=4.523, P=0.033;χ²=4.909, P=0.027). After treatment, the levels of vascular endothelial growth factor (VEGF) in ascites of the experimental group and the control group were significantly lower than those before treatment [(80.33±1.41) pg/mlvs. (310.45±3.35) pg/ml,t=449.884,P<0.001; (135.68±1.60) pg/mlvs. (310.46±3.09) pg/ml,t=499.281,P<0.001], and after treatment, the VEGF level in the experimental group decreased more significantly than that in the control group (t=-134.907,P<0.001). Patients in the experimental group and the control group tolerated the treatment well, and there were no significant differences in the incidences of adverse reactions such as hypertension (11.11%vs.3.70%,χ²=0.270,P=0.603), neutropenia (14.81%vs.11.11%,χ²<0.001,P>0.999), peripheral neuropathy (3.70%vs.0,χ²<0.001,P>0.999), diarrhea (7.41%vs.3.70%,χ²<0.001,P>0.999), nausea (3.70%vs.0,χ²<0.001,P>0.999), epistaxis (7.41%vs.0,χ²=0.519,P=0.471) or albuminuria (3.70%vs.0,χ²<0.001,P>0.999) between the two groups.ConclusionIntraperitoneal perfusion of bevacizumab combined with chemotherapy is superior to simple chemotherapy in the treatment of malignant peritoneal adhesion caused by ovarian cancer.

Key words:Ovarian neoplasms,Angiogenesis inhibitors,Peritoneal adhesion,Malignant bowel obstruction,Bevacizumab

郑静, 姚胜, 沈文洁, 孙志佳, 赵辉, 付艳, 高珂, 杜楠. 腹腔灌注贝伐珠单抗联合白蛋白紫杉醇和卡铂治疗卵巢癌所致癌性腹腔粘连的临床探讨[J]. 国际肿瘤学杂志, 2021, 48(11): 660-665.

Zheng Jing, Yao Sheng, Shen Wenjie, Sun Zhijia, Zhao Hui, Fu Yan, Gao Ke, Du Nan. Clinical study of intraperitoneal infusion of bevacizumab combined with albumin paclitaxel and carboplatin in carcinomatous peritoneal adhesion from ovarian cancer[J]. Journal of International Oncology, 2021, 48(11): 660-665.

图/表5

表1

两组卵巢癌合并癌性粘连性肠梗阻患者的临床特征比较[例(%)]"

临床特征
绝经情况
是	25(92.59)	24(88.89)	<0.001	>0.999
否	2(7.41)	3(11.11)
KPS评分
80~100分	2(7.41)	1(3.70)	<0.001	>0.999
60~80分	25(92.59)	26(96.30)
腹部CT(腔外占位>1 cm)
腹腔积液及两个以上部位转移	16(59.26)	18(66.67)	0.318	0.573
大网膜及肠系膜转移	25(92.59)	24(88.89)	0.220	0.639
肝转移	5(18.52)	6(22.22)	0.114	0.735
多发性结肠及小肠受累	22(81.48)	23(85.19)	0.133	0.715
肿瘤类型
浆液性囊腺癌	21(77.78)	22(81.48)	0.114	0.735
黏液性囊腺癌	6(22.22)	5(18.52)
病理分级
Ⅰ级	1(3.70)	1(3.70)
Ⅱ级	4(14.81)	3(11.11)	0.170	0.982
Ⅲ级	18(66.67)	19(70.37)
未知/未明确	4(14.81)	4(14.81)
二次手术后	10(37.04)	12(44.44)	0.307	0.580

表1

组别	显效	有效	无效	治疗有效
对照组(n=27)	5(18.52)	11(40.74)	11(40.74)	16(59.26)
试验组(n=27)	10(37.04)	13(48.15)	4(14.81)	23(85.19)
χ²值				4.523
P值				0.033

表2

组别	CR	PR	SD	PD	总有效
对照组(n=27)	1(3.70)	11(40.74)	10(37.04)	5(18.51)	12(44.44)
试验组(n=27)	3(11.11)	17(62.96)	5(18.52)	2(7.41)	20(74.07)
χ²值					4.909
P值					0.027

表3

组别	治疗前	治疗后	t值	P值
对照组(n=27)	310.46±3.09	135.68±1.60	499.281	<0.001
试验组(n=27)	310.45±3.35	80.33±1.41	449.884	<0.001
t值	-0.007	-134.907
P值	0.995	<0.001

表4

不良反应 (≥2级)	试验组 (n=27)	对照组 (n=27)	χ²值	P值
高血压	3(11.11)	1(3.70)	0.270	0.603
中性粒细胞减少	4(14.81)	3(11.11)	<0.001	>0.999
周围神经病变	1(3.70)	0(0)	<0.001	>0.999
腹泻	2(7.41)	1(3.70)	<0.001	>0.999
恶心	1(3.70)	0(0)	<0.001	>0.999
鼻出血	2(7.41)	0(0)	0.519	0.471
蛋白尿	1(3.70)	0(0)	<0.001	>0.999

表5

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