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

Abstract

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

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.

Figures/Tables5

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

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

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

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

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

References15

[1]	Pignata S, C Cecere S, Du Bois A, et al. Treatment of recurrent ovarian cancer[J]. Ann Oncol, 2017, 28(suppl_8): viii51-viii56. DOI: 10.1093/annonc/mdx441.
[2]	Mariani A, Wang C, Oberg AL, et al. Genes associated with bowel metastases in ovarian cancer[J]. Gynecol Oncol, 2019, 154(3):495-504. DOI: 10.1016/j.ygyno.2019.06.010. doi:S0090-8258(19)31321-6pmid:31204077
[3]	牛茜, 阳志军. 靶向药物治疗上皮性卵巢癌的研究进展[J]. 中国肿瘤生物治疗杂志, 2020, 27(12):1423-1430. DOI: 10.3872/j.issn.1007-385x.2020.12.018.
[4]	Herr D, Sallmann A, Bekes I, et al. VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5[J]. Gynecol Oncol, 2012, 127(1):210-216. DOI: 10.1016/j.ygyno.2012.05.002. doi:10.1016/j.ygyno.2012.05.002
[5]	Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer[J]. N Engl J Med, 2006, 354(1):34-43. DOI: 10.1056/NEJMoa052985. doi:10.1056/NEJMoa052985
[6]	Elit L, Oliver TK, Covens A, et al. Intraperitoneal chemotherapy in the first-line treatment of women with stage Ⅲ epithelial ovarian cancer: a systematic review with metaanalyses[J]. Cancer, 2007, 109(4):692-702. DOI: 10.1002/cncr.22466. doi:10.1002/(ISSN)1097-0142
[7]	洪进德, 郭卉, 徐秀兰. 新辅助化疗与洛铂术中腹腔灌注在卵巢癌中的效果评价及机制研究[J]. 当代医学, 2021, 27(11):105-106. DOI: 10.3969/j.issn.1009-4393.2021.11.043.
[8]	Dean E, Khoja L, Clamp A, et al. Malignant bowel obstruction in advanced ovarian cancer[J]. Future Oncol, 2017, 13(6):513-521. DOI: 10.2217/fon-2016-0431. doi:10.2217/fon-2016-0431
[9]	Luo JC, Yamaguchi S, Shinkai A, et al. Significant expression of vascular endothelial growth factor/vascular permeability factor in mouse ascites tumors[J]. Cancer Res, 1998, 58(12):2652-2660. pmid:9635593
[10]	Tewari KS, Burger RA, Enserro D, et al. Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer[J]. J Clin Oncol, 2019, 37(26):2317-2328. DOI: 10.1200/JCO.19.01009. doi:10.1200/JCO.19.01009
[11]	Lengyel E. Ovarian cancer development and metastasis[J]. Am J Pathol, 2010, 177(3):1053-1064. DOI: 10.2353/ajpath.2010.100105. doi:10.2353/ajpath.2010.100105pmid:20651229
[12]	Masoumi Moghaddam S, Amini A, Morris DL, et al. Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer[J]. Cancer Metastasis Rev, 2012, 31(1-2):143-162. DOI: 10.1007/s10555-011-9337-5.
[13]	Dizon DS, Sill MW, Gould N, et al. Phase Ⅰ feasibility study of intraperitoneal cisplatin and intravenous paclitaxel followed by intraperitoneal paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: a gynecologic oncology group study[J]. Gynecol Oncol, 2011, 123(2):182-186. DOI: 10.1016/j.ygyno.2011.07.016. doi:10.1016/j.ygyno.2011.07.016pmid:21820161
[14]	Landrum LM, Java J, Mathews CA, et al. Prognostic factors for stage Ⅲ epithelial ovarian cancer treated with intraperitoneal chemotherapy: a Gynecologic Oncology Group study[J]. Gynecol Oncol, 2013, 130(1):12-18. DOI: 10.1016/j.ygyno.2013.04.001. doi:10.1016/j.ygyno.2013.04.001pmid:23578540
[15]	Jaaback K, Johnson N, Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer[J]. Cochrane Database Syst Rev, 2016(1): CD005340. DOI: 10.1002/14651858.CD005340.pub4.