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

• Published in: Journal of oncology pharmacy practice 2011-06, Vol.17 (2), p.136-140
• Main Authors: Tuffaha, Haitham W, Al Omar, Suha
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - blood; Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - blood; Cancer therapies; Child; Drug therapy; Drug Therapy, Combination; Drugs, Investigational - therapeutic use; Enzyme Therapy; Female; gamma-Glutamyl Hydrolase - therapeutic use; Hemodialysis; Humans; Jordan; Kidney diseases; Leucovorin - therapeutic use; Mandibular Neoplasms - drug therapy; Methotrexate - administration & dosage; Methotrexate - adverse effects; Methotrexate - blood; Oncology; Osteosarcoma - drug therapy; Toxicity; Treatment Outcome; Vitamin B Complex - therapeutic use
• ISSN: 1078-1552; 1477-092X
• DOI: 10.1177/1078155209348720

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.