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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 concentrations and side effects of high-dose methotrexate (HD-MTX) chemotherapy in patients with osteosarcoma who were treated at the same treatment center in different periods, and to explore whether they can be increased by increasing the dosage of the drug Peak plasma concentration in order to achieve the purpose of improving the efficacy; at the same time compare the safety of different periods. Methods The patients with osteosarcoma receiving HD-MTX chemotherapy in this treatment center were divided into two groups according to the different treatment periods. The first group included 150 patients between January 2002 and December 2007, and received HD-MTX chemotherapy 159 patients, the average dose of drug was 7.62g / m ~ 2 (6.07 ~ 9.57g / m ~ 2); the second group was 104 patients between July 2009 and August 2010, 155 person-time, the average dose of drug is 9.73g / m ~ 2 (7.38 ~ 10.86g / m ~ 2). The peak plasma concentration and toxicity were compared and analyzed statistically. Results The peak plasma concentration of group 1 was 683.65μmol / L (99.00 ~ 1252.84μmol / L), while the group 2 was increased to an average of 1061.65μmol / L (524.02 ~ 1764.14μmol / L) 0.05). Toxic side effects, group 2 compared with the first group, leukopenia and thrombocytopenia is more serious, the difference was significant, according to the WHO anti-tumor drug toxicity grading standards to reach 3 to 4 ratio increased by 4.7 and 0.6 percentage points (P <0.05). However, there was no significant difference between the two groups in the test results of liver and kidney function (P> 0.05). Two groups of patients through the corresponding hydration alkalosis urine, leucovorin (CF) detoxification treatment, granulocyte colony stimulating factor (G-CSF) and liver protection drug treatment, close monitoring of plasma concentration, 24h urine output, urine pH Value, chemotherapy after blood, liver and kidney function and other indicators, no cases of death due to MTX chemotherapy, and can be followed by chemotherapy or surgery and other treatment. Conclusion The treatment center in recent years by increasing the dose of MTX drugs, effectively raising the peak plasma concentration, while liver and kidney dysfunction did not significantly aggravated, although bone marrow suppression has aggravated, but by granulocyte colony stimulating factor (G- CSF) can be quickly returned to normal, does not affect the normal follow-up of chemotherapy, to prove that this dose of HD-MTX chemotherapy in the clinical use is safe and effective.