摘要
目的观察和确证腔内应用重组人血管内皮抑制素注射液(恩度)和/或顺铂治疗恶性胸腹腔积液的有效性和安全性。方法 2011年1月至2014年1月,在全国14家大型医院肿瘤中心开展前瞻性、随机、平行对照、多中心的Ⅲ期临床研究(Clinical Trials.gov注册号:NCT01327235)。入选中等量以上恶性胸腹腔积液患者,随机分为A组(恩度单药组)、B组(顺铂单药组)和C组(恩度联合顺铂组)。3组均在充分穿刺抽液或引流后给药。A组腔内注射恩度,45 mg/次(胸腔)或60mg/次(腹腔);B组腔内注射顺铂,40 mg/次;C组为上述两种药物联合应用,剂量相同;3组给药时间均为d1、d4、d7,连用3次为1个疗程。参照WHO标准,严密观察客观缓解率(ORR)、疾病进展时间(TTP)、生活质量(QOL)以及Karnofsky功能状态评分(KPS),并评价安全性。结果全分析集(FAS)共纳入317例,其中A组105例,B组104例,C组108例;符合方案集(PPS)共纳入275例,其中A组98例,B组89例,C组88例。FAS和PPS分别有298例和273例可评价疗效。FAS中A、B、C3组的ORR分别为48.51%、46.39%和63.00%(P=0.0373),两两比较,C组较A、B组高(P=0.0189)。其中,既往无腔内治疗、胸腔积液、女性、无全身化疗、积液初治、充分引流、血性积液以及非胃癌来源的患者,应用恩度具有更好的ORR(P<0.05或P<0.01)。对于血性积液,A、C组ORR分别为71.05%和80.00%,均显著优于B组的45.16%(P=0.0090);其中,对于血性胸腔积液,A、C组ORR分别为71.42%和88.88%,均显著优于B组的40.00%(P=0.0013)。A、B、C组的中位TTP分别为68.869天、44.951天和69.030天(P=0.0121);两两比较,A、C组的中位TTP均长于B组(P=0.0240,P=0.0046)。第3次和第6次用药后,A组QOL评分和KPS评分获得改善人群的比例均显著高于B、C组(P<0.05或P<0.01)。安全性方面,317例均进入安全分析集分析。A组不良事件发生率显著低于B组(P=0.0005),B、C组之间差异无统计学意义(P=0.2866)。结论采用恩度腔内�
Objective To evaluate the clinical efficacy and safety of intra-pleural injection of recombinant human endostatin （endostar） and/or cisplatin in treatment of malignant hydrothorax and ascites. Methods The multicenter, randomized controlled study was conducted in 14 Chinese nationwide large hospitals from January 2011 to January 2014（ Clinical Trials： NCT01327235. ）. A total of 317 patients with more than moderate amount of pericardial effusion malignant hydrothorax and ascites were randomly divided into group A （endostar group, n= 105）, group B （cisplatin group, n= 104） and group C （endostar combined eisplatin group, n= 108）. After puncture and drainage, endostar 45 mg per time by intrathoraeie injection or 60 mg per time by intraperitoneal injection was performed in group A. Cisplatin, 40 mg per time by intra-pleural injection on day 1,4 and 7, was administrated in group B. Endostar and cisplatin were administrated in group C. All three groups of patients were administrated on day 1, 4 and 7, and three times as a course. The main outcomes were objective response rate （ORR）, time to disease progression （TTP）, quality of life （QOL） and Karnofsky performance status （ KPS）, as well as the drug safety. Results A total of 317 patients were included in full analysis set （FAS） （group A with 105 eases, group B with 104 eases, group C with 108 eases）, and 275 patients were included in per-protocol set （PPS） （group A with 98 eases, group B with 89 eases, group C with 88 eases）. There were 298 eases and 273 cases qualified for e- valuation on drug efficacy in FAS and PPS respectively. There was a significant difference in ORR among three groups （A： 48.51%, B： 46. 39%, C： 63.00%, P=0. 0373）, and ORR was higher in group C than that in groups A and B （P=0. 0189）. Patients without intracavitary treatment history, with hydrothorax, female, without systemic chemotherapy, with initial treatment on effusion, with suffi- cient drainage, with hemorrhagic effusion and
出处
《临床肿瘤学杂志》
CAS
2017年第3期193-202,共10页
Chinese Clinical Oncology
