骨肉瘤患者大剂量甲氨蝶呤化疗方案中影响甲氨蝶呤排泄延迟的相关因素分析

Analysis of related factors affecting delayed excretion of methotrexate in high-dose methotrexate chemotherapy regimen for osteosarcoma patients

目的 探究骨肉瘤患者大剂量甲氨蝶呤化疗方案中影响甲氨蝶呤排泄速度以及药物不良反应发生的因素。方法 回顾性统计分析28例骨肉瘤患者97个大剂量甲氨蝶呤化疗周期中甲氨蝶呤排泄情况,肝损伤、肾损伤、骨髓抑制等药物不良反应发生情况,以及患者血液中甲氨蝶呤0、24、48、72 h浓度和血液中白蛋白水平,分析各因素的相关性。结果 骨肉瘤患者大剂量甲氨蝶呤化疗中,当甲氨蝶呤峰浓度(0 h,C_(max))≥700μmol·L^(-1)时排泄延迟风险增加:甲氨蝶呤峰浓度(0 h,C_(max))≥700μmol·L^(-1)时延迟排泄发生率为23.21%,峰浓度<700μmol·L^(-1)组的延迟排泄发生率为5.00%,差异有统计学意义(P<0.05),但当峰浓度≥1 000μmol·L^(-1)时排泄延迟风险没有进一步增加:甲氨蝶呤峰浓度≥1 000μmol·L^(-1)组的延迟排泄发生率为16.00%,峰浓度<1 000μmol·L^(-1)组的延迟排泄发生率为15.49%,差异无统计学意义(P>0.05)。甲氨蝶呤血液峰浓度与肝损伤以及骨髓抑制等重要药物不良反应的发生无显著相关性。患者白蛋白水平偏低与患者发生骨髓抑制有显著相关性:骨髓抑制组和无骨髓抑制组白蛋白水平分别为(39.1±3.4)和(41.2±4.0) g·L^(-1),差异有统计学意义(P<0.05)。结论 骨肉瘤患者大剂量甲氨蝶呤化疗中,不应以降低峰浓度的方式预防延迟排泄和药物不良反应,患者白蛋白水平是患者发生骨髓抑制的重要影响因素。

Objective To explore the factors that affect the excretion rate of methotrexate and the occurrence of adverse reactions in highdose methotrexate chemotherapy for osteosarcoma patients.Methods Retrospectively analyzed methotrexate excretion,liver injury,kidney injury,bone marrow suppression and other adverse drug reactions in 97high-dose methotrexate chemotherapy cycles of 28 patients with osteosarcoma.The concentration of methotrexate in the blood at 0,24,48,72 h and the level of white protein in the blood were also analyzed.Results When the peak concentration of methotrexate(0 h,C_(max)) ≥700 μmol·L^(-1) the risk of excretion delay increases:the incidence was23.21% in group with C_(max)≥700 μmol·L^(-1),and it was 5.00% in group with C_(max) <700 μmol·L^(-1),(P <0.05),but when the peak concentration was≥1 000 μmol·L^(-1),the risk of delayed excretion did not increase further:the incidence was 16.00% in group with C_(max)≥1 000 μmol·L^(-1),and it was 15.49% in group with C_(max) <1 000 μmol·L^(-1),(P>0.05).Methotrexate blood C_(max)has no significant correlation with the occurrence of important adverse reactions such as liver injury and bone marrow suppression.There was significant correlation between low serum albumin level and bone marrow suppression in patients.The average albumin level in group with bone marrow suppression was(39.1±3.4) g · L^(-1),which in without bone marrow suppression group was(41.2±4.0) g · L^(-1)(P <0.05).Conclusion During high-dose methotrexate chemotherapy in patients with osteosarcoma,delayed excretion and adverse reactions should not be prevented by lowering the peak concentration.The albumin level of patients is an important factor affecting the occurrence of bone marrow suppression.