肺癌支气管动脉卡铂灌注化疗与栓塞的药代动力学研究

Treatment of lung cancer with bronchial arterial carboplatin infusion and embolization:a pharmaco-kinetic study

目的比较肺癌治疗中单纯卡铂灌注与卡铂灌注加栓塞进行药动学研究,并观察不良反应及疗效,明确灌注加主干栓塞优于单纯灌注。方法 30例中晚期支气管肺癌患者,分为两组,各15例。A组经支气管动脉灌注卡铂300mg(其他药物依病理类型定),灌注后即加明胶海绵栓塞;B组只行单纯灌注。抽取术后不同时间点静脉血,测定血液中铂离子浓度,绘制铂离子时间平均浓度曲线,计算曲线下面积(AUC)。观察术后反应,检验术前3d、术后10d血常规,摄术前3d及术后1个月X线胸片或CT。结果①A、B两组外周血铂离子时间浓度曲线均为单峰逐渐下降的曲线,峰值分别为(2.71±0.09)mg/kg和(4.37±0.28)mg/kg,两组差异有统计学意义(P<0.05);两组AUC分别为(23.81±1.82)mg·h/kg和(32.74±5.00)mg·h/kg,差异有统计学意义(P<0.05)。②A组术后化疗反应恶心、呕吐程度较B组轻(P<0.05);A组白细胞减少发生率低于B组(P<0.05)。③术后1个月有效率A组明显优于B组(P<0.05)。结论与单纯卡铂灌注相比,灌注加主干栓塞可有效提高和保持肿瘤组织内铂浓度,降低外周血中铂浓度,从而提高疗效。

Objective For the treatment of lung cancer,the clinical significance of simultaneous performing of bronchial arterial infusion chemotherapy （BAI） and bronchial arterial embolization （BAE） has not yet clarified. This study aims to compare the therapeutic results,including pharmacokinetics,side effects and clinical effectiveness,between simple BAI and the combination of BAI with BAE in an attempt to prove that BAI together with BAE might be superior to simple BAI. Methods Thirty patients with advanced pulmonary cancer were randomly divided into two groups with 15 patients in each group. Bronchial arterial perfusion chemotherapy with carboplatin （300 mg） immediately followed by BAE with Gelfoam was performed in the patients of group A （study group）,while only bronchial arterial perfusion chemotherapy with carboplatin （300 mg） was employed in the patients of group B （control group）. Venous blood samples were collected at different points of time after the procedure （0 and 20 minutes,1,12,24 and 48 hours）,the concentrations of platinum in samples were measured and the mean concentration-time curves of the platinum were drawn,based on which the areas under concentration-time curve （AUC） were calculated. Clinical response after the treatment was observed. The routine blood tests were carried out three days before and ten days after the therapy. Chest X-ray or thoracic CT scan was conducted three days before and one month after the treatment. The side-effects and the clinical effectiveness were recorded and the results were compared between two groups. Results （1） The concentration-time curve presented as a gradually declining curve in both group A and group B,with the peak concentration of platinum being （2.71 ± 0.09） mg / kg and （4.37 ± 0.28） mg / kg,respectively. The difference between group A and group B was statistically significant （P 〈0.05）. The AUC0-48 h was （23.81 ± 1.82） mg.h / kg in group A and （32.74 ± 5.00） mg.h / kg in group B,the difference between two groups was significant （P 〈0.05）. （2） The side-effects such as nausea and vomiting in Group A were much lighter than that in group B （P 〈0.05）. The occurrence of neutropenia in the group A was significantly lower than that in group B （P 〈0.05）. （3） One month after the therapy,the total clinical efficacy of Group A was much better than that of group B （P 〈0.05）. Conclusion In comparison with simple BAI,BAI combined with BAE can reliably increase the concentration of platinum in tumor tissue and effectively hold the higher concentration of platinum in tumor tissue for a long time,while the peripheral concentration of platinum is decreased,in this way the clinical therapeutic efficacy is markedly improved.