DDP在肺癌介入化疗和静脉化疗中药动学和毒副反应的比较研究

Comparative study of toxic reactions and pharmacological dynamics of DDP administrated by trans-arterial injection and intravenous infusion in patients with NSCLC

目的 从DDP在肺癌支气管动脉灌注化疗及静脉全身化疗中外周血药浓度变化的比较研究着手,重点分析化疗药物在肺癌介入治疗中的全身毒副反应及其药动学基础。方法选择2000年4月～2002年5月在我院介入科住院,经病理证实为晚期NSCLC初诊病人60例,经随机分组,试验组(A组)接受DDP支气管动脉灌注化疗,对照组(B组)接受DDP静脉全身化疗。A组30例,MMC10mg/m^2,VDS3mg/m^2,分别溶于20ml生理盐水静脉推注,DDP80mg/m^2,溶于生理盐水250ml经支气管动脉灌注30min。B组30例,MMC10mg/m^2,VDS3mg/m^2,分别溶于20ml生理盐水静脉推注,DDP80mg/m^2,溶于生理盐水250ml经静脉滴注30min。病人于DDP给药开始后5min、15min、30min、1h、2h、4h、8h、12h、24h、48h经外周静脉留置管取血(2ml/次),置于抗凝干燥试管内,经高效液相色谱仪(HPLC)检测病人血样DDP浓度,绘制时间浓度曲线。化疗期间观察记录化疗药物的全身毒副反应情况。结果①A组与B组均在给DDP开始30min时达到血药浓度曲线最高点,峰值血药浓度B组高于A组,有明显统计学差异(P<0.001)。②在测量的时间段内,B组曲线下面积明显高于A组,有明显统计学差异(P<0.05)。③临床观察,A组恶心、呕吐及肾功能损害等毒副反应比B组轻,统计学上有显著性差异(P<0.05)。

Objective Through a comparative analysis serum concentration of DDP administrated by intra ?arterial injection and intravenous infusion in patients with non - small cell lung cancer (NSCLC), the whole body toxic reactions and the pharmacological mechanism of chemotherapy agents administrated by bronchial artery infusion (BAI) was studied. Methods In total 60 patients with advanced NSCLC confirmed by pathology were randomly enrolled into two groups in this study. The 30 patients in group A were treated by BAI chemotherapy with DDP at the dose of 80mg/m2 within 30 min, while MMC at the dose of lOmg/ m2 and VDS at the dose of 3mg/ m2 were given intravenously. Patients in group B was given intravenous chemotherapy of the same components as that given in group A. Blood samples was collected at 5min, 15min, 30min, Ih, 2h, 4h, 8h, 24h and 48h from the beginning of DDP infusion. High performance liquid chromatography (HPLC) was used to measure DDP concentration in blood samples and a time - concentrate curve was drawn. During chemotherapy, the side - effects were investigated. Results (1) Both group A and B reached a peak concentration at 30 min. Peak concentration value of group B is higher than that of group A. There was a statistical difference of peak concentration between group A and B (P < 0.001) (2) AUC value of group B is higher than that of group A, with a statistical difference ( P < 0. 05) . (3) The incidence of gastrointestinal complication and kidney function damage has a statistical difference between group A and B (P = 0. 002 and 0.028 respectively). Conclusion The side-effects is slighter in BAI chemotherapy than in IV chemotherapy in the treatment of NSCLC.