Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients

Abstract

Background Glucarpidase rapidly reduces methotrexate plasma concentrations in patients experiencing methotrexate-induced renal dysfunction. Debate exists regarding the role of glucarpidase in therapy given its high cost. The use of reduced-dose glucarpidase has been reported, and may allow more institutions to supply this drug to their patients. This report explores the relationship between glucarpidase dosage and patient outcomes in pediatric oncology patients. Methods The authors evaluated data from 26 patients who received glucarpidase after high-dose methotrexate. Decrease in plasma methotrexate concentrations and time to renal recovery were evaluated for an association with glucarpidase dosage, which ranged from 13 to 90 units/kg. Results No significant relationship was found between glucarpidase dosage (units/kg) and percent decrease in methotrexate plasma concentrations measured by TDx (P >0.1) or HPLC (P >0.5). Patients who received glucarpidase dosages <50 units/kg had a median percent reduction in methotrexate plasma concentration of 99.4% (range, 98–100) measured by HPLC compared to a median percent reduction of 99.4% (range, 77.2–100) in patients who received ≥50 units/kg. Time to SCr recovery was not related to glucarpidase dosage (P >0.8). Conclusions The efficacy of glucarpidase in the treatment of HDMTX-induced kidney injury was not dosage-dependent in this retrospective analysis of pediatric oncology patients. Pediatr Blood Cancer 2015;62:1518–1522.

Management of Patients with Acute Methotrexate Nephrotoxicity with High‐Dose Leucovorin

“…This fact was reflected in another study where a similar rate of renal recovery was observed, as in other reports . Although in three other studies the median MTX levels at 48–96 hours were higher, the range of MTX levels was similar to the levels in this study …”

“…More recent experience with the management of HDMTX‐associated renal dysfunction and delayed MTX excretion in a larger group of patients treated in a similar fashion are reviewed and reported in this article. The results were also compared with other studies that used glucarpidase . The relationship between the degree of AKI and serial MTX levels, the lack of correlation between MTX levels at 24 hours and subsequent time points, and the influence of additional cytotoxic chemotherapy in the development of severe (grade III or higher) myelosuppression are also analyzed in this article.…”

Glucarpidase for the Treatment of Methotrexate‐Induced Renal Dysfunction and Delayed Methotrexate Excretion

“…Scott et al report that the time to recovery of renal function for patients treated with lower dose glucarpidase was the same as that reported in the prior experience. [1,3] It is also exactly the same the time reported in a cohort of patients with methotrexate-induced renal dysfunction and delayed methotrexate excretion treated without glucarpidase.…”

“…Scott et al report that the time to recovery of renal function for patients treated with lower dose glucarpidase was the same as that reported in the prior experience. [1,3] It is also exactly the same the time reported in a cohort of patients with methotrexate-induced renal dysfunction and delayed methotrexate excretion treated without glucarpidase.[4] This is unsurprising, since restoration of normal renal function requires prolonged flow of alkaline urine through the collecting system to resolubilize methotrexate and is completely unaffected by administration of glucarpidase.The use of glucarpidase in the treatment of methotrexate-induced renal dysfunction and delayed methotrexate excretion is associated with high cost, need to interrupt life preserving administration of leucovorin, loss of reliability in monitoring methotrexate concentration to guide therapy, and is unnecessary. It does not alter the need to provide appropriate leucovorin rescue.…”

“…To the Editor: Scott et al report that lower doses of glucarpidase are as effective as the recommended dose for the treatment of methotrexate-induced renal dysfunction and delayed methotrexate excretion. [1] An accompanying editorial by Widemann acknowledges the lower doses used by Scott et al were associated with outcomes similar to those observed in patients treated with higher doses. [2] An alternative explanation for the observations, not considered by the authors of the report or the editorial, is that glucarpidase is unnecessary for the treatment of methotrexateinduced renal dysfunction and delayed methotrexate excretion and therefore the dose is irrelevant.…”