Glucarpidase rescue in a patient with high-dose methotrexate-induced nephrotoxicity

摘要

Purpose. To describe the successful use of glucar- pidase (carboxypeptidase G2) in the treatment of high-dose methotrexate-induced nephrotoxicity in a patient with osteosarcoma.Summary. 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 metho- trexate. 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 leveldropped 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.Conclusion. Glucarpidase is a safe and effective agent in the management of high-dose methotrexate-induced nephrotoxicity and delayed methotrexate elimination. J Oncol Pharm Practice (2011) 17: 136-140.