基于兔VX2原位移植肺癌模型评价多西他赛脂质体疗效和安全性

目的 评价多西他赛脂质体(DTX-LP)的远期疗效和不良反应.方法 建立兔VX2原位移植肺癌模型,分别静脉给予荷瘤兔空白脂质体(BLA-LP)、多西他赛注射剂(DTX-IN,2.7 mg/kg)、DTX-LP高剂量(0.9 mg/kg)、DTX-LP中剂量(0.3 mg/kg)以及DTX-LP低剂量(0.1 mg/kg)治疗4周期,记录兔生存时间并作生存分析,考察兔存活期间体质量及白细胞计数变化率,食欲减退、腹泻、肠道出血发生率,实验兔死亡后作大体解剖,评估主要脏器的组织病理损害程度.结果 BLA-LP组,DTX-IN组,DTX-LP高、中、低剂量组兔的中位生存时间分别为28、35、49、34、32 d.生存曲线经Log-Rank检验,DTX-LP高剂量组分别与BLA-LP组、DTX-IN组比较,差异有统计学意义(P =0.001,P=0.005).上述各治疗组兔的平均体质量变化率分别为(-23.03±7.99)％、(-11.25 ±9.67)％、(-1.48±6.36)％、(-2.08±14.39)％和(-17.27±18.41)％;白细胞计数累积变化率分别为(-3.53±18.17)％、(-52.78±12.50)％、(-16.56±10.21)％、(-22.19±10.70)％和(-15.37±14.14)％.DTX-IN组和DTX-LP高剂量组食欲减退的发生率分别为83.3％和50.0％;BLA-LP组、DTX-IN组及DTX-LP高、中、低剂量组腹泻发生率分别为16.7％、66.7％、33.3％、16.7％、16.7％;DTX-IN组肠道出血发生率83.3％.病理检查结果显示DTX-LP高剂量组的心、肝、脾、肺、肾组织无明显异常,DTX-IN组上述脏器均有不同程度的病理损害.结论 DTX-LP高剂量组明显延长VX2肺癌兔中位生存期,且不良反应轻微.

Efficacy and safety evaluation of docetaxel liposome in a rabbit model bearing orthotopically transplanted VX2 tumor

Objective To evaluate the long-term efficacy and safety of docetaxel liposome(DTX-LP) in a rabbit model of lung cancer.Methods Thirty rabbit models of lung cancer established by orthotopic transplantation of VX2 tumor tissues were randomized in 5 equal groups to receive intravenous injections of blank liposome (BLA-LP),docetaxel (DTX-IN,2.7 mg/kg),or DTX-LP at high (0.9 mg/kg),moderate (0.3 mg/kg) or low (0.1 mg/kg) doses once a week for 4 consecutive weeks,and the survival time of the rabbits was recorded.The survival of the rabbits in each group was estimated using Kaplan-Meier analysis and analyzed with Log-rank test.The changes in body weight and leukocyte count of the rabbits were observed,and the incidence of anorexia,diarrhea and intestinal bleeding were evaluated.After the rabbits died,the heart,liver,spleen,lungs and kidneys were dissected for histopathological examinations.Restlts The median survival time of the rabbits was 28 d in BLA-LP group,35 d in DTX-IN group,49 d in high-dose DTX-LP group,34 d in moderate-dose DTX-LP group and 32 d in low-dose DTX-LP group.The survival rate of the rabbits was significantly higher in high-dose DTX-LP group than in BLA-LP group (P =0.001) and DTX-IN group (P =0.005).The percent change in the body weight in the 5 groups was (-23.03 ± 7.99) ％,(-11.25 ±9.67)％,(-1.48 ±6.36)％,(-2.08 ±14.39)％ and (-17.27 ±18.41)％,respectively,and that of leukocyte count was (-3.53 ±18.17)％,(-52.78 ±12.50)％,(-16.56±10.21)％,(-22.19 ± 10.70) ％ and (-15.37 ± 14.14％),respectively.The incidence of anorexia was 83.3％ in DTX-IN group and 50.0％ in high-dose DTX-LP group.The incidence of diarrhea was 16.7％,66.7％,33.3％,16.7％ and 16.7％ in the 5 groups,respectively,and intestinal bleeding occurred in DTX-IN group was 83.3％.Histological examination revealed obvious pathological changes in the heart,liver,spleen,lungs and kidneys in DTX-IN group but not in high-dose DTX-LP group.Conclusion Treatment with high-dose DTX-LP significantly prolongs the survival of tumor-bearing rabbits with only mild adverse effects.