雾化吸入粒细胞-巨噬细胞集落刺激因子治疗肺转移癌的临床研究  

Clinical study of inhaled GM-CSF for patients with metastatic lung cancer to the lungs

作　　者：吴登斌[1,2] 王文萍[1] 高晶晶[1] 王忠帅[2] 艾春玲[2] 高广营 

机构地区：[1]辽宁中医药大学附属医院临床药品试验基地,沈阳110032 [2]鞍山曙光医院肿瘤放疗科

出　　处：《肿瘤研究与临床》2009年第9期608-608,609,610,613,共4页Cancer Research and Clinic

摘　　要：目的研究雾化粒细胞-巨噬细胞集落刺激因子（GM—CSF）作用于原发于肺部肿瘤肺转移癌的药物毒性和治疗的可行性。方法采用GM—CSF三个剂量递增水平的试验设计，每日2次雾化连续7d休息7d的方案。若未观察到药物的毒性反应，休息7d后再进行下一个剂量水平的试验。结果7例患者中的6例完成60、120和240μg3个剂量水平的雾化试验。雾化GM—CSF前后白细胞数和粒细胞百分比数差异无统计学意义。另外9例患者接受240μgGM—CSF的7d雾化方案治疗2～6个月，无一例患者观察到药物的毒性反应。2例肺腺癌双肺转移和1例小细胞肺癌双肺转移，病情进展，其余6例患者病情稳定2～6个月，全部患者未发生药物的不良反应。结论雾化GM—CSF治疗原发性肺癌的肺转移，是一种耐受性较好的生物治疗，也显示出一定的抗肿瘤作用。Objective To evaluate the feasibility of granulocyte macrophage-colony stimulating factor （GM-CSF） delivery, to the lung using an aerosol in patients with metastatic lung cancer to the lungs. Methods A Phase I dose escalation study inhaled GM-CSF at three dose levels as twice-a-day×7 days schedule. Blood counts were checked at the beginning and end of each week of GM-CSF nebulization. If no toxicity was encountered, in-patients rested for 7 days and then were inhaled at the next dose level. Results Six of seven patients were all dose escalated from 60 μg/dose twice-a-dayx7 days, to 120 μg/dose twice-a-day×7 days, then 240 μg/dose twice-a-day×7 days, one of the patients with cerebral hemorrhage was removed from the clinical trials, and no toxicity was seen. Comparison of inhaled GM-CSF of day 0 and day 7 blood leukocyte counts and percentage of neutrophils, it showed no significant difference in analysis of blood count data at the beginning and end of nebulization used paired t tests for each dose level. The other 9 patients received an additional 2-6 months of intermittent aerosol GM-CSF at 240 μg dose level without side effect. Two patients with bilateral lung metastases of lung adenocarcinoma had a progress disease after 2-2.5 months of aerosol GM-CSF. One patient with lung metastasis of SCLC had a progressive disease after 2 months of aerosol GM- CSF, the other 6 patients had stabilization of pulmonary metastases for 2-6 months. Conclusion Aerosol delivery of GM-CSF may achieve effective immunological antitumor action in the metastases tumor to lungs, and this therapy is feasible and possibly effective and worthy of further study.

关 键 词：粒细胞巨噬细胞集落刺激因子 肺肿瘤 肿瘤转移 投药 吸入 

分 类 号：R734.2[医药卫生—肿瘤]