重组人血管内皮抑素治疗恶性浆膜腔积液的临床研究

Clinical study of endostar on malignant cavity effusion

目的观察重组人血管内皮抑素注射液(恩度)治疗恶性浆膜腔积液的有效性和安全性,初步探讨不同的恩度联合治疗模式对疗效的影响。方法 2008年12月至2011年3月共收治31例恶性浆膜腔积液患者应用恩度治疗,其中恶性胸腔积液10例、腹腔积液18例和多浆膜腔积液3例。31例均采用腔内局部治疗,包括恩度单药14例、恩度联合羟基喜树碱(HCPT)8例和恩度联合顺铂(PDD)9例,具体方法:恩度45～60mg/次,q3d(d1、d4、d7);HCPT10mg/次或PDD40mg/次,q3d(d2、d5、d8)。31例患者中联合局部热疗17例,于腔内治疗后30min行局部热疗42℃45min;联合含恩度的静脉全身治疗13例,15mg/日静滴。腔内局部治疗连续3次为1周期,至多接受2个周期治疗。按照WHO胸腹水评价标准和NCI2CTC AE3.0分级标准分别评估疗效和毒副反应。结果腔内恩度单药和联合化疗治疗的有效率分别为42.9%(CR 3例,PR 3例)和76.5%(CR1例,PR 12例),腔内治疗联合局部热疗的有效率为76.5%(CR 4例,PR 9例),3组差异无统计学意义(P=0.075)。27例获有效或稳定的患者中静脉全身治疗含恩度组(n=12)和不含恩度组(n=15)的中位疾病进展时间(TTP)分别为110天和30天(χ2=6.911,P=0.009);腔内恩度单药组(n=11)和腔内恩度联合化疗组(n=16)的中位TTP分别为35天和85天(χ2=3.862,P=0.041)。腔内治疗联合局部热疗组(n=15)和未联合局部热疗组(n=12)的中位TTP分别为85天和60天(χ2=0.919,P=0.338)。全组生活质量改善率为77.4%(24/31)。3～4级毒副反应主要为白细胞减少、血小板减少、恶心呕吐和乏力,发生率分别为9.7%(3/31)、16.1%(5/31)、9.7%(3/31)和19.4%(6/31),无治疗相关性死亡。结论恩度单药腔内治疗恶性浆膜腔积液有效,同时联合细胞毒药物腔内化疗的疗效更优,两者具有协同作用;腔内局部治疗配合含恩度的静脉全身治疗优于单纯局部治疗,腔内局部治疗与局部热疗联合亦有增效的倾向,有待深入观察。

Objective To observe the efficacy and safety of rh-endostatin injection（YH-16,endostar） on malignant cavity effusion and explore the influences of different combination modalities on efficacy initially.Methods Thirty-one patients with malignant cavity effusion diagnosed at our hospital during December 2008 to March 2011 were analyzed retrospectively,including 10 cases of malignant pleural effusion,18 cases of malignant ascites and 3 cases of multi-cavity effusion.All patients were given cavity infusion,including 14 cases of endostar monotherapy,8 cases of endostar with HCPT,and 9 cases of endostar with PDD.The dosage was taken as follow： endostar 45-60mg per time on d1,d4,d7;HCPT 10mg or PDD 40mg each time on d2,d5,d8.Thirty minutes after cavity infusion,17 patients were administrated regional thermotherapy with 42℃ for 45min.Thirteen in 31 were given endostar systematic treatment,15mg per day iv.Three consecutive cavity infusion was a cycle,and all patients were treated no more than 2 cycles.The efficacy was evaluated strictly according to WHO criteria and safety according to NCI CTC AE 3.0 version criteria.Results The response rates of patients given cavity infusion of endostar monotherapy and endostar in combination with HCPT or PDD were 42.9%（3 patients had CR,3 patients had PR）,76.5%（1 patient had CR,12 patients had PR） respectively;the response rate of patients given cavity infusion in combination with regional thermotherapy was 76.5%（3 patients had CR,9 patients had PR）,with no significance（P=0.075）.Among 27 responders,median TTP of endostar contained systematic treatment（n=12） and uncontained group（n=15） were 110 days vs.30 days（χ2=6.911,P=0.009）;median TTP of endostar monotherapy（n=11） and cytotoxic agents combination group（n=16） were 35days vs.85 days（χ2=3.862,P=0.041）;median TTP of thermotherapy combination or not were 85days vs.60 days（χ2=0.919,P=0.338）,respectively.The improvement rate of QOL was 77.4%（24/31）.G3/4 toxicities mainly included neutropenia（9.7%,3/31）,thrombocytopenia（16.1%,5/31）,nausea/vomiting（9.7%,3/31） and fatigue（19.4%,6/31）.No treatment-related death occurred.Conclusion Due to synergetic effect,the efficacy of endostar combined with cytotoxic agents on malignant cavity effusion was superior to that of endostar monotherapy.Cavity infusion combining with endostar contained systematic treatment is superior to regional cavity infusion alone.Meanwhile combination with thermotherapy has a beneficial tendency and is worth further clinical observation.