大剂量甲氨蝶呤化疗后毒副反应对比研究  

A comparative study of the toxic side reactions caused by high-dose methotrexate chemotherapy

作　　者：马珂[1] 赵海涛[1] 张清[1] 

机构地区：[1]北京积水潭医院骨肿瘤科,100035

出　　处：《中国骨与关节杂志》2012年第2期132-135,共4页Chinese Journal of Bone and Joint

摘　　要：目的对不同时期在同一治疗中心进行治疗的骨肉瘤患者接受大剂量甲氨蝶呤(HD-MTX)化疗后的血药浓度峰值及毒副反应进行比较,进而探讨是否可以通过增加药物剂量来提高血药浓度峰值,以达到改善疗效的目的 ;同时比较不同时期的安全性情况。方法将在本治疗中心接受HD-MTX化疗的骨肉瘤患者按照不同治疗时期分为2组,第1组为2002年1月至2007年12月之间的患者150例,行HD-MTX化疗总计159人次,药物剂量平均为7.62g/m^2(6.07～9.57g/m^2);第2组为2009年7月至2010年8月之间的患者104例,行HD-MTX化疗总计155人次,药物剂量平均为9.73g/m^2(7.38～10.86g/m^2)。比较其血药浓度峰值及毒副反应情况,进行统计学分析。结果第1组血药浓度峰值为平均683.65μmol/L(99.00～1252.84μmol/L);第2组提高至平均1061.65μmol/L(524.02～1764.14μmol/L),差别具有显著性意义(P<0.05)。毒副反应方面,第2组与第1组相比,白细胞和血小板减少方面较为严重,差别具有显著性意义,按照WHO抗肿瘤药毒性分级标准,达到3～4级的比例分别上升了4.7和0.6个百分点(P<0.05);而肝肾功能方面的化验结果 ,两组之间差别则并无显著性意义(P>0.05)。两组患者经过相应的水化碱化尿液、亚叶酸钙(CF)解毒治疗、粒细胞集落刺激因子(G-CSF)及保肝药物治疗,严密监测血药浓度、24h尿量、尿pH值、化疗后血常规、肝肾功能等指标,均无因MTX化疗而死亡的病例,并能够按时进行后续化疗或手术等治疗。结论本治疗中心近几年通过提高MTX药物剂量,有效地提高了其血药浓度峰值,同时肝肾功能损害并无显著加重,骨髓抑制虽有所加重,但通过粒细胞集落刺激因子(G-CSF)治疗,可迅速恢复正常,不影响后续化疗正常进行,证明了此剂量下的HD-MTX化疗在临床中使用是安全有效的。Objective To compare the peak plasma concentration and toxic side reactions after the osteosarcoma patients received the high-dose methotrexate （HD-MTX） chemotherapy in the same treatment center in different periods, and then to investigate the feasibility of improving the peak plasma concentration by increasing the drug dose for improving the efficacy. Meanwhile the safety in different periods was compared. Methods The osteosarcoma patients who underwent the HD-MTX chemotherapy in our treatment center were divided into 2 groups according to the different treatment periods. From January 2002 to December 2007, the first group of 150 patients received the HD-MTX chemotherapy with an average dose of 7.62g/m2 （range; 6.07-9.57g/m2） and 159 person-time. From July 2009 to August 2010, the second group of 104 patients received the HD-MTX chemotherapy with an average dose of 9.73g/m2 （range; 7.38-10.86g/m2） and 155 person-time. The peak plasma concentration and toxic side reactions were compared and then the statistical analysis was conducted. Results The mean peak plasma concentration of the first group was 683.65μmol/L （range; 99.00-1252.84μmol/L） and that of the second group increased to an average of 1061.65μmol/L （range; 524.02-1764.14μmol/L）. The differences were statistically significant （P〈0.05）. In terms of the toxic side reactions, leukocytes and platelets decreased significantly in the second group comparing with the first group. The differences were statistically significant. According to the World Health Organization （WHO） toxicity grading standard of antineoplastic agents, the ratio of grade 3-4 sincreased by 4.7% and 0.6% respectively （P〈0.05）. However, the test results of the hepatic and renal function showed that the differences between the 2 groups were not statistically significant （P〉0.05）. The patients of both groups underwent the antidotal treatment of hydration and alkalization of urine and calcium folinate （CF） and the drug therapy of granulocyte c

关 键 词：骨肉瘤 大剂量甲氨蝶呤 化疗 副反应 

分 类 号：R738.1[医药卫生—肿瘤]