重组人血小板生成素对化疗所致血小板减少症的预防方案优化研究

Optimization of prophylactic regimen of recombinant human thrombopoietin for chemotherapy-induced thrombocytopenia

目的探讨重组人血小板生成素(rhTPO)对吉西他滨联合卡铂(GC)或吉西他滨联合顺铂(GP)方案化疗相关血小板减少症(CIT)二级预防的优化方案。方法2019年3月—2020年6月,在内蒙古自治区人民医院、河南大学肿瘤医院共招募非小细胞肺癌(NSCLC)患者60例,此60例患者行GP/GC方案化疗,前1个化疗周期中血小板计数最低值<50×10^(9)·L^(−1),且经治疗已恢复正常,60例患者随机分为对照组和试验组,每组各30例,对照组患者在下1个化疗周期第2、4、6、9天预防性给予重组人血小板生成素(rhTPO),试验组患者在下1个化疗周期第3、4、6天预防性给予rhTPO,监测两组患者的血小板计数变化,并进行对比分析。结果试验组和对照组3度以上血小板减少症的发生率分别为40%、30%,两组比较差异无统计学意义;试验组血小板最低值为(38±13)×10^(9)·L^(−1),对照组为(45±17)×10^(9)·L^(−1),两组对比差异无统计学意义;试验组和对照组化疗后血小板计数低于100×10^(9)·L^(−1)的持续时间分别为(9±3)、(7±4)d,两组比较差异显著(P<0.05);试验组和对照组化疗后血小板低于50×10^(9)·L^(−1)的持续时间分别为(4±3)、(3±2)d,两组比较差异无统计学意义。预防用药结束后,试验组有14例患者继续给予rhTPO治疗,rhTPO中位使用支数为3支(1~7支);对照组有13例患者继续给予rhTPO治疗,rhTPO中位使用支数为3支(1~6支),两组非参数秩和检验,差异无统计学意义。试验组有1例、对照组有2例患者血小板过低或伴有明显出血倾向,给予输注血小板。结论rhTPO在吉西他滨联合铂类化疗方案的第3、4、6天3 d用药方案相较传统4 d方案,疗效及安全性无明显差异,但能减少患者住院天数,降低治疗费用。

Objective To explore the optimal scheme of recombinant human thrombopoietin(rhTPO)for the secondary prevention of chemotherapy-related thrombocytopenia(CIT)with gemcitabine combined with carboplatin(GC)or gemcitabine combined with cisplatin(GP).Methods From March 2019 to June 2020,60 patients with non-small cell lung cancer(NSCLC)were recruited from the people's Hospital of Inner Mongolia Autonomous Region and the Cancer Hospital of Henan University.These 60 patients underwent GP/GC chemotherapy.The lowest platelet count in the first chemotherapy cycle was less than 50×10^(9)·L^(−1) and returned to normal after treatment.60 patients were randomly divided into control group and experimental group,the patients in the control group were given rhTPO on the 2nd,4th,6th and 9th day of the next chemotherapy cycle,the patients in the experimental group were given rhTPO prophylactically on the 3rd,4th and 6th day of the next chemotherapy cycle,the changes of platelet count in the two groups were monitored and compared.Results The incidence of thrombocytopenia above grade three in the experimental group and the control group were 40%and 30%respectively,and there was no significant difference between two groups.The lowest platelet value in the experimental group was(38±13)×10^(9)·L^(−1),the control group was(45±17)×10^(9)·L^(−1),there was no significant difference between the two groups.The duration of platelet count was lower than 100×10^(9)·L^(−1) after chemotherapy of the experimental group and the control group was(9±3)and(7±4)d,respectively,there was significant difference between two groups(P<0.05).The duration of platelet count was lower than 50×10^(9)·L^(−1) after chemotherapy of the experimental group and the control group was(4±3)and(3±2)d,respectively,and there was no significant difference between the two groups.After the end of preventive medication,14 patients in the experimental group continued to be treated with rhTPO,and the median number of rhTPO was three branch(1—7 branchs),13 patients in the control group continued to be treated with rhTPO,and the median number of rhTPO was three branches(1—6 branches),there was no significant difference between the two groups by nonparametric rank sum test.One patient in the experimental group and two patients in the control group were given platelet transfusion because of low platelet or obvious bleeding tendency.Conclusion Compared with the traditional four day regimen,optimal scheme of rhTPO administered on days 2rd,4th,and 6th of gemcitabine combined with platinum chemotherapy regimen has no significant difference in efficacy and safety,but it can reduce the length of hospital stay and treatment cost.