Effective high-dose methotrexate toxicity reversal using fixed-dose glucarpidase in obese patients: a case series

This case report and literature review present two instances of delayed methotrexate clearance in individuals who were successfully managed using fixed dosing versus weight-based dosing of glucarpidase. These cases, along with existing literature, support the use of fixed-dose glucarpidase as an alternative to weight-based dosing for delayed methotrexate clearance.

Patient 1: a 26-year-old obese African American male with newly diagnosed osteosarcoma of the right distal fibula underwent his first cycle of neoadjuvant chemotherapy with MAP. Following the administration of doxorubicin and cisplatin, the patient developed acute kidney injury, with increased serum creatinine. He was admitted for high-dose methotrexate administration. Leucovorin rescue began 24 hours after high-dose methotrexate infusion. Twenty-five hours post-infusion, the patient had an elevated serum creatinine and methotrexate levels. A fixed dose of glucarpidase (2000 units) was administered, resulting in rapidly declining methotrexate levels and patient discharge. Patient 2: a 77-year-old obese white male with primary central nervous system lymphoma was admitted for cycle 3 of high-dose methotrexate and rituximab as first-line treatment. His pretreatment comorbidities included chronic kidney disease, coronary artery disease, hypertension, pulmonary hypertension, and chronic obstructive pulmonary disease. Following rituximab and high-dose methotrexate administration, nephrology was consulted owing to elevated creatinine. Leucovorin rescue began 24 hours after high-dose methotrexate treatment. On day 2, creatinine remained elevated with a post-dose methotrexate level indicating potential delayed clearance. A fixed dose of glucarpidase (2000 units) was administered, resulting in rapidly declining methotrexate levels and patient discharge. Cycle 4 was performed without complications, but cycle 5 required a fixed dose of glucarpidase owing to potential delayed clearance, resulting in rapidly declining methotrexate levels and patient discharge.

In patients receiving high-dose methotrexate therapy requiring glucarpidase therapy, transitioning to a fixed dosing approach has significant cost-saving implications for institutions.