CAJ | 학술논문

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.
목적:관찰세포감멸술가복강열관주화료(CRS+HIPEC)연합파향신약 PDOX 치료위암복막암(PC)적료효화안전성.방법:장 VX2류세포주입40지신서란토위두부점막하,제성위암 PC 모형,수궤분4조(n=10):Control 조관찰자연병정;HIPEC 조행 CRS+HIPEC;PDOX 조화 DOX 조행 CRS+HIPEC 연합화료(PDOX 50.0 mg/kg,DOX 5.0 mg/kg).결과:모형성공솔100%(40/40).Control 조중위생존기23.0 d(95%CI:19.9~26.1 d),HIPEC 조41.0(36.9~45.1)d,PDOX 조58.0(39.6~54.4)d, DOX 조65.0(44.1~71.9)d.HIPEC 조생존기교 Control 조연장70.0%이상(P<0.001),PDOX 조화 DOX 조교 HIPEC 조연장40.0%이상(P=0.029、P=0.021).DOX조화료후WBC、PLT저우HIPEC조(P<0.05),각조간혈액학지표차이무통계학의의(P>0.05).결론:재CRS+HIPEC기출상,연합파향신약PDOX가진일보연장위암PC모형생존기,독성무명현증가.
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 (docetaxel 10.0mg and carboplatin 50.0 mg in 250 mL normal saline, at 42.5 ± 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 every 4 d for 5 cycles) after CRS+HIPEC. The CRS+HIPEC regimen was performed for a total of 8 d, while the systemic chemotherapy was initiated 16 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 lactate dehydrogenase (LDH) between the 2 groups at the same time point. The values of white blood cell and platelet were significantly lower in the DOX than in the HIPEC group, after the systemic chemotherapy (P<0.05). Conclusion: The regimen of CRS plus HIPEC could bring survival benefits to the gastric cancer rabbit model with PC. Furthermore, the addition of molecular targeted therapy with PDOX could bring about better survival benefits with more satisfactory drug safety.