Tuffaha Haitham W, Al Omar Suha
King Hussein Cancer Center, P.O. Box 1269 Aljubeiha, Amman, 11941 Jordan.
J Oncol Pharm Pract. 2011 Jun;17(2):136-40. doi: 10.1177/1078155209348720. Epub 2009 Oct 15.
To describe the successful use of glucarpidase (carboxypeptidase G2) in the treatment of high-dose methotrexate-induced nephrotoxicity in a patient with osteosarcoma.
A 12-year-old female patient who had been diagnosed with low-grade right mandibular osteosarcoma was started on a protocol of cisplatin plus doxorubicin alternating with high-dose methotrexate. Following her first dose of methotrexte, she developed acute renal failure and higher than expected 24h methotrexate level of 478μM/L. High-dose leucovorin rescue was started with vigorous hydra- tion and urine alkalinization together with two sessions of hemodialysis. Because her methotrexate level was persistently high, the investigational drug glucarpidase was administered. Methotrexate level dropped from 65 to 16.3 μM/L after a single dose of glucarpidase measured by fluorescence polarization immunoassay. Leucovorin and urine alkalinization were continued until day 17 when the patient's kidney function normalized and methotrexate level reached 0.05 μM/L. The patient tolerated glucarpidase well without any significant adverse events.
Glucarpidase is a safe and effective agent in the management of high-dose methotrexate-induced nephrotoxicity and delayed methotrexate elimination.
描述羧肽酶G2（葡糖羧肽酶）成功用于治疗骨肉瘤患者大剂量甲氨蝶呤诱导的肾毒性。
一名12岁女性患者被诊断为低度右下颌骨肉瘤，开始接受顺铂加阿霉素与大剂量甲氨蝶呤交替使用的方案。在她首次服用甲氨蝶呤后，出现急性肾衰竭，24小时甲氨蝶呤水平高于预期，达478μM/L。开始大剂量亚叶酸钙解救，同时进行积极补液、尿液碱化以及两次血液透析。由于她的甲氨蝶呤水平持续居高不下，于是给予研究药物羧肽酶G2。通过荧光偏振免疫测定法测得，单次服用羧肽酶G2后，甲氨蝶呤水平从65μM/L降至16.3μM/L。继续给予亚叶酸钙和尿液碱化治疗，直到第17天患者肾功能恢复正常，甲氨蝶呤水平降至0.05μM/L。患者对羧肽酶G2耐受性良好，未出现任何严重不良事件。
羧肽酶G2在治疗大剂量甲氨蝶呤诱导的肾毒性和甲氨蝶呤清除延迟方面是一种安全有效的药物。
