重组人血小板生成素预防非小细胞肺癌化疗后血小板减少的临床观察

Clinical observation of recombinant human thrombopoietin in the treatment of thrombocytopenia in patients with non small cell lung cancer induced by chemotherapy

目的探讨重组人血小板生成素(rhTPO)预防非小细胞肺癌(NSCLC)化疗后血小板减少的临床疗效。方法收集2012年9月—2015年2月中国医科大学附属盛京医院第一肿瘤科收治经病理学确诊的NSCLC患者36例,均经吉西他滨联合顺铂或卡铂化疗(GP或GC)第1周期2周内发生Ⅱ~Ⅲ度血小板减少。采用随机数字表法均分为A、B、C、D 4组,每组9例,并继续进行3个周期相同方案化疗。A组于化疗前第1、3、5天及化疗第2、4、6、9天给予rhTPO(1μg·kg^(-1)·d^(-1)),B组于化疗前第1、3天及化疗第2、4、6、9天给予rhTPO(1μg·kg^(-1)·d^(-1)),C组于化疗前第1天及化疗第2、4、6、9天给予rhTPO(1μg·kg^(-1)·d^(-1)),D组未予以rhTPO,分别监测各组患者的血小板最低值、血小板<50×10~9/L的持续天数、血小板恢复至≥75×10~9/L及≥100×10~9/L的天数、因血小板降低所致下一周期化疗延误的天数、血小板输注的次数和用量,并进行对比分析,同时观察记录不良反应。结果 4组间血小板最低值、血小板<50×10~9/L的持续天数、血小板恢复至≥75×10~9/L时间、血小板恢复至≥100×10~9/L时间以及延误下一周期化疗的天数等各项指标比较差异均有统计学意义(F=14.993、9.563、22.285、9.011、12.310,P均=0.000),A组优于B、C组,B、C组优于D组;在血小板输注的用量上,A组更占优势,分别与C组与D组比较,差异有统计学意义(q=-3.888、-6.782,P=0.006、0.000)。各组均无严重不良反应。结论对于既往GP或GC化疗导致的严重血小板减少的NSCLC患者,预防性给予rhTPO可降低血小板减少的严重程度,并缩短血小板恢复时间,减少血小板输注量,其中以化疗前5天开始的间歇性预防策略疗效最佳,总体不良反应轻微,耐受性好。

Objective To explore the therapeutic effect and safety of prophylactic use of recombinant human thrombo -poietin （ rhTPO） in the treatment of thrombocytopenia in patients with non small cell lung cancer （ NSCLC） induced by chem-otherapy.Methods Pathologically confirmed NSCLC patients , with grade II or III thrombocytopenia in two weeks , after the first cycle of chemotherapy with gemcitabine and cisplatin or carboplatin , were randomly divided into four groups （ A, B, C, D）, and underwent three identical cycles of chemotherapy , from September 2012 to February 2015, in China Medical Univer-sity.Group A received subcutaneous injection of rhTPO （1 μg· kg^-1 · d^-1 ） on the 1st, 3rd, 5th day before chemotherapy , and the 2nd, 4th, 6th, 9th day of cycle.Group B received subcutaneous injection of rhTPO （1μg· kg^-1· d^-1） on the 1st, 3rd day before chemotherapy , and the 2nd, 4th, 6th, 9th day of cycle.Group C received subcutaneous injection of rhTPO （1μg· kg^-1· d^-1） on the 1st day before chemotherapy, and the 2nd, 4th, 6th, 9th day of cycle.No rhTPO was received in group D.The efficacy and adverse effects were observed .Results A total of 36 patients were enrolled , with 9 patients in each group.Compared with group D , the patients in group A , B, C were showed a significantly higher nadir platelet count , shorter duration of thrombocytopenia and recovery of platelet count , less days delayed （ P 〈0.05）.Compared with group B and C, the patients in group A showed a significantly higher nadir platelet count , shorter duration of thrombocytopenia （ 〈50 ×10 ^9/L）, and recovery of platelet count （≥75 ×10^9/L） （ P 〈0.05）.The difference between four groups was statistically signifi-cant（ F =14.993, F =9.563, F =22.285, F =9.011, F =12.310,all the P value was 0.000）.Compared with group C and group D , group A was statistically significant in less platelet transfusion .No serious adverse effects was observed in all groups.Conclusion For NSCLC patients with severe thrombocytopenia caused by GP or GC chemotherapy , prophylactic use of rhTPO can significantly reduce the degree and duration of thrombocytopenia , reduce the treatment times of platelet transfu-sion, and ensure the accuracy of the time and dosage of chemotherapy .The intermittent preventive strategies , which began with the 5 days before chemotherapy , were the best choice .The adverse effects of rhTPO were mild and well tolerated .