大剂量甲氨蝶呤治疗骨肉瘤血药浓度监测结果分析

摘要

目的 分析大剂量甲氨蝶呤治疗骨肉瘤血药浓度特点及对甲酰四氢叶酸钙(CF)使用的指导意义,以预防和减轻毒副反应.方法 选取2012年1月至2014年10月在南京大学医学院附属南京鼓楼医院住院的骨肉瘤手术前后患者67例,依据甲氨蝶呤用药剂量分为甲氨蝶呤8 g/m2组(34例)和甲氨蝶呤10 g/m2组(33例).采用酶增强免疫分析(EMIT)法监测化疗后0、24、48、72 h甲氨蝶呤血药浓度(Cx,x=0、24、48、72),分析Cx与患者年龄、性别、用药剂量的关系,观察2组患者的毒副反应发生情况,并记录C24≥5.0 μmol/L和/或C48≥0.5 μmol/L和/或C72≥0.2μmol/L的患者增加使用CF解救的次数和剂量.结果 C0和C24甲氨蝶呤8g/m2组与甲氨蝶呤10 g/m2组比较差异有统计学意义[(548.01±127.03) μmol/L比(839.48±113.09) μmol/L、(4.61±1.46) μmol/L比(5.79±3.01) μmol/L,P＜0.05],C48和C722组比较差异无统计学意义(P＞0.05).在同一剂量组中,不同年龄和不同性别患者之间,各时点Cx差异无统计学意义(P＞0.05);C24和/或C48和/或C72高于安全值的患者,甲氨蝶呤8 g/m2组有11例(32.4％),甲氨蝶呤10 g/m2组有16例(48.5％);甲氨蝶呤10 g/m2组毒副反应发生率和程度与甲氨蝶呤8 g/m2组差异无统计学意义(P＞0.05);与甲氨蝶呤8 g/m2组相比,甲氨蝶呤10 g/m2组CF的用量和解救次数明显增加,差异有统计学意义[(132±66)mg比(104±31)mg、(7.2± 1.9)次比(6.5±1.5)次,P＜0.05].结论 在通常6～ 12 g/m2的用量中,适当增加大剂量甲氨蝶呤的用量可以明显提高甲氨蝶呤血药浓度的峰值,但也会延迟甲氨蝶呤的清除,依据监测结果适时调整CF的用量和用法,可以预防和减轻毒副反应.%Objective To analyze serum concentration monitoring of high-dose methotrexate (HD-MTX)for rational use of calcium folinate (CF) in treating osteosarcoma.Methods Totally 67 osteosa-rcoma patients with or without operation from January 2012 to October 2014 were divided into MTX 8 g/m2 group (34 cases) and MTX 10 g/m2 group (33 cases).The serum concentrations of MTX in 67 cases were determined by enzyme-enhancement immunoassay technique 0, 24, 48 and 72 h after treatment (Cx, x =0, 24, 48, 72).The relation among Cx, age, gender and dosages was analyzed;the toxicity of MTX was observed;the times and dosages of CF for rescue treatment in patients with C24 ≥5.0 μmol/L and/or C48 ≥0.5 μmol/L and/or C72 ≥0.2 μmol/L were recorded.Results C0 and C24 in MTX 8 g/m2 group were significantly lower than those in MTX 10 g/m2 group [(548.01 ±127.03) μmol/L vs (839.48 ±113.09) μmol/L, (4.61 ±1.46) μmol/L vs (5.79 ±3.01) μmol/L] (P ＜ 0.05);C48 and C72 showed no significant differences between the two groups (P ＞ 0.05).Cx at different time points was not significantly different among patients of different age and gender in both groups(P ＞ 0.05).Totally 11 cases (32.4％) in MTX 8 g/m2 group, 16 cases (48.5％) in MTX 10 g/m2 group had C24 and/or C4s and/or C72 above safety value.In MTX 10 g/m2 group, the dosages and times of CF for rescue treatment were significantly increased compared with those in MTX 8 g/m2 group [(132 ± 66) mg vs (104 ± 31) mg, (7.2 ± 1.9) times vs (6.5 ± 1.5) times, P ＜ 0.05].There was no significant difference regarding toxicity between two groups.Conclusion On the basis of general dosage of 6 ～ 12 g/m2 , the peak serum concentration of HD-MTX is significantly increased, the removal of MTX is delayed with increase of dosage;adjusting the dosage and usage of CF according to the results of serum concentrations monitoring of MTX, the toxicity can be prevented and reduced.