(121) Glucarpi-CAP: A retrospective chart review of 1000 unit glucarpidase dosing for methotrexate rescue

Poster Abstract: Authors: Sydney Ertz, PharmD, PGY2 Oncology Pharmacy Resident; Joseph Bubalo, PharmD, BCOP, Oncology Pharmacist

Location: OHSU Health System; Portland, OR

Background/Rationale: Methotrexate is a common treatment for multiple cancer types. Methotrexate is given at toxic doses followed by leucovorin rescue and high drug levels can result in acute kidney injury (AKI).1-3 Glucarpidase is a recombinant enzyme approved for the management of toxic methotrexate levels in patients with impaired renal function experiencing delayed clearance.4 Glucarpidase hydrolyzes the terminal residue from extracellular methotrexate into inactive metabolites which can be excreted regardless of renal function.4 Glucarpidase dose per prescribing information is 50 units per kilogram in a single dose with no defined dosage maximum.4 A retrospective study examined glucarpidase ranging from 13 to 90 units per kilogram in 26 patients with elevated methotrexate levels. In this study, there was no significant relationship found between the percent decrease in methotrexate plasma concentration and glucarpidase dosage. Time to serum creatinine recovery was also not correlated to glucarpidase dosing.5

At Oregon Health & Science University, the standard of care protocol caps doses at 1 vial (1000 units) of glucarpidase since there is a lack of evidence to prove that higher doses of glucarpidase result in greater clinical benefit.6 Due to the high cost of glucarpidase, capping the dose at 1 vial provides cost savings for the patient and the institution. This study will assess the effectiveness of using a capped dose of glucarpidase for methotrexate clearance in patients with renal impairment and toxic drug levels.

Methods: This is a single-center retrospective chart review of patients who received glucarpidase following methotrexate in the inpatient setting from January 1st, 2012 to April 1st 2023. Data will be collected from the institution’s electronic medical record. Patients who meet inclusion criteria will be enrolled, and data will be collected from the date of methotrexate infusion to the end of their hospital admission. Each patient’s medical record will be reviewed by investigators for methotrexate treatment regimen, glucarpidase dosing, pertinent clinical history (disease, other chemotherapy, etc.), demographics, relevant laboratory values, and adverse effects associated with the chemotherapy treatment.
Outcomes: The primary outcome will be the reduction in methotrexate levels. Secondary outcomes include renal recovery, survival, and adverse effects of glucarpidase.

Results and

Conclusion: Results of this study will provide evidence on the utility of a capped 1000 unit glucarpidase dose for methotrexate rescue. Not yet available, will be included on final poster

References (must also be included in final poster): 1. Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist. 2006;11(6):694-703. doi:10.1634/theoncologist.11-6-694
2. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High-Dose Methotrexate. Oncologist. 2016;21(12):1471-1482. doi:10.1634/theoncologist.2015-0164
3. Perazella MA, Moeckel GW. Nephrotoxicity from chemotherapeutic agents: clinical manifestations, pathobiology, and prevention/therapy [published correction appears in Semin Nephrol. 2011 May;31(3):317]. Semin Nephrol. 2010;30(6):570-581. doi:10.1016/j.semnephrol.2010.09.005
4. Glucarpidase (Voraxaze) [package insert]. Brentwood, TN: BTG International Incorporated.
5. Scott JR, Zhou Y, Cheng C, et al. Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients. Pediatr Blood Cancer. 2015;62(9):1518-1522. doi:10.1002/pbc.25395
6. OHSU Health Glucarpidase Use Policy for Pediatric and Adult Oncology. MCN HC-CKT-125-POL. Rev 052721. Effective 5/7/2021.