Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma
Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma
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DOI：
10.1007/s00280-010-1259-3
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发表时间：
2010-11-01
影响因子：
3
通讯作者：
Goldwasser, Francois
中科院分区：
文献类型：
--
作者：
Mir, Olivier;Ropert, Stanislas;Goldwasser, Francois
为了评价高剂量甲氨蝶呤（HDMTX）在高碱化和不过度水合的情况下给药的可靠性和肾脏安全性，骨肉瘤患者接受HDMTX（8-12 g/m2）4小时输注。在HDMTX前输注高渗8.4%碳酸氢钠，然后每日一次，持续3天。在第4小时（Cmax）、第24小时、第48小时和第72小时测量甲氨蝶呤血清浓度。每次排尿时测量尿pH值。在第1、3和8天评估血清肌酐。26例患者（中位年龄：18岁，范围：15-25岁）共接受了344个周期的HDMTX治疗，其中16例患者在门诊接受治疗。所有患者的尿pH值始终高于7.5。在31个周期（9%）中观察到1级肌酐血症毒性，在1例患者中观察到2级肌酐毒性。未观察到急性重度肾毒性发作。从基线至治疗结束，未观察到血清肌酐和计算的肌酐清除率显著恶化（P = 0.74）。主要的肾外毒性是H48的碱化相关低钾血症。高碱化似乎是一种有效和可靠的方法，以防止HDMTX的急性肾毒性，并允许其在门诊设置安全管理。
To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyper-hydration.Patients with osteosarcoma received HDMTX (8-12 g/m(2)) as a 4-h infusion. Hypertonic 8.4% sodium bicarbonate was infused prior to HDMTX, then once daily for 3 days. Methotrexate serum concentrations were measured at hour 4 (Cmax), hour 24, hour 48, and hour 72. Urinary pH was measured on each miction. Serum creatinine was assessed on days 1, 3, and 8.Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344 cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH remained constantly higher than 7.5 in all patients. Grade 1 creatininemia toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was observed in one patient. No episode of acute severe nephrotoxicity was observed. No significant worsening was observed in serum creatinine and calculated creatinine clearance from baseline to the end of therapy (P = 0.74). The main extra-renal toxicity was alkalinization-related hypokalemia from H48. No re-hospitalization was required.Hyper-alkalinization appears an efficient and reliable method to prevent the acute renal toxicity of HDMTX and allows its safe administration in the outpatient setting.