细胞减灭术加腹腔热灌注化疗联合靶向新药PDOX治疗胃癌腹膜癌  

Experimental Study on the Efficacy and Safety of Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy Combined with Molecular Targeted Therapeutic Regimen Ac-Phe-Lys-PABC-DOX(PDOX) for Treating Peritoneal Carcinomatosis of Gastric Cancer

作　　者：唐利[1] 王群[1] 袁静萍[1] 邵丽华[1] 梅列军[1] 王林伟[1] 曾卫娟[1] 刘少平[1] 李雁[1] 

机构地区：[1]武汉大学中南医院肿瘤科,肿瘤生物学行为湖北省重点实验室,湖北省癌症临床研究中心,武汉市430071

出　　处：《中国肿瘤临床》2012年第22期1719-1725,共7页Chinese Journal of Clinical Oncology

基　　金："重大新药创制"科技重大专项(编号:2009ZX09301);国家自然科学基金创新群体资助项目(编号:20621502);国家大学生创新性实验计划项目(编号:081048646)资助~~

摘　　要：目的:观察细胞减灭术加腹腔热灌注化疗(CRS+HIPEC)联合靶向新药PDOX治疗胃癌腹膜癌(PC)的疗效和安全性。方法:将VX2瘤细胞注入40只新西兰兔胃窦部黏膜下,制成胃癌PC模型,随机分4组(n=10):Control组观察自然病程;HIPEC组行CRS+HIPEC;PDOX组和DOX组行CRS+HIPEC联合化疗(PDOX 50.0 mg/kg,DOX 5.0 mg/kg)。结果:模型成功率100%(40/40)。Control组中位生存期23.0 d(95%CI:19.9～26.1 d),HIPEC组41.0(36.9～45.1)d,PDOX组58.0(39.6～54.4)d,DOX组65.0(44.1～71.9)d。HIPEC组生存期较Control组延长70.0%以上(P<0.001),PDOX组和DOX组较HIPEC组延长40.0%以上(P=0.029、P=0.021)。DOX组化疗后WBC、PLT低于HIPEC组(P<0.05),各组间血液学指标差异无统计学意义(P>0.05)。结论:在CRS+HIPEC基础上,联合靶向新药PDOX可进一步延长胃癌PC模型生存期,毒性无明显增加。Objective： This work aimed to study the efficacy and safety of cytoreductive surgery （CRS） plus hyperthermic intra -peritoneal chemotherapy （HIPEC） combined with targeting anti-tumor drug Ac-Phe-Lys- PABC-DOX （PDOX） for treating the gastric cancer rabbit models with peritoneal carcinomatosis （PC）. Methods：VX2 tumor cells were injected into the gastric sub-mucosa of 40 adult male New Zealand rabbits using a laparotomic inoculation technique and laparoscopy in order to construct the gastric cancer rabbit model with PC. The rabbits were randomly divided into 4 groups： the Control group （ n=10 ） without any treatment, the HIPEC group （n=10 ） receiving CRS plus HIPEC （docetaxel10 .0mg and carboplatin 50 .0 mg in250 mL normal saline, at42 .5 ± 0.5℃for 30 min）, the PDOX group （n=10 ） receiving systemic chemotherapy with PDOX 50 .0 mg/kg （10 .0 mg/kg every 4 d for 5 cycles） after CRS＋HIPEC, and the DOX group （n=10） receiving systemic chemotherapy with DOX 5.0 mg/kg （1.0 mg/kg every4 d for 5 cycles） after CRS＋HIPEC. The CRS＋HIPEC regimen was performed for a total of 8 d, while the systemic chemotherapy was initiated16 d after model construction. The primary endpoint was overall survival （OS）, and the secondary endpoint was safety profile.Results：Rabbit PC model was successfully established in all animals （100%,40 /40 ）. The median （95 % confidence interval [CI]） survivals were 23 .0 d （19 .9 d to 26 .1 d） in the Control group, 41 .0 d （36 .9 d to 45 .1 d） in the HIPEC group,58 .0 d （39 .6 d to 54 .4 d） in the PDOX group, and 65 .0 d （44 .1 d to 71 .9 d） in the DOX group. Compared with the Control group, the OS was extended by at least 70% in the HIPEC group （P〈0.001）. Compared with the HIPEC group, the OS was extended by at least 40 % in the PDOX and DOX groups （P=0.029, PDOX vs. HIPEC; P=0.021, DOX vs. HIPEC）. There were no differences in the blood cell count, liver and kidney functions, creatine kinase （CK）, CK-MB, and

关 键 词：胃癌腹膜癌靶向治疗 细胞减灭术腹腔热灌注化疗 

分 类 号：R735.2[医药卫生—肿瘤]