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Updated: Feb 16, 2026

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
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Delayed Methotrexate Clearance Despite Carboxypeptidase-G2 (Glucarpidase) Administration in 2 Patients With Toxic

Kirk D Wyatt1, Jeffrey Cooper2, Katherine Scott3

  • 1Mayo Clinic, Rochester, MN.

Journal of Pediatric Hematology/Oncology
|December 15, 2017
PubMed

Insights

High-dose methotrexate can harm kidneys in osteosarcoma patients. Glucarpidase helps clear toxic methotrexate levels, but some patients may need repeated doses and dialysis for kidney injury.

Area of Science:

  • Oncology
  • Pharmacology
  • Nephrology

Background:

  • High-dose methotrexate is a standard osteosarcoma treatment.
  • Methotrexate-induced nephrotoxicity is a significant clinical challenge.
  • Carboxypeptidase-G2 (glucarpidase) is an FDA-approved enzyme for toxic methotrexate level reduction.

Observation:

  • This report details the compassionate use of glucarpidase in two patients with osteosarcoma experiencing delayed methotrexate clearance.
  • Both patients exhibited prolonged kidney injury despite initial glucarpidase administration.
  • Supportive care, including dialysis, was crucial for managing renal complications.

Findings:

  • Patients with severe methotrexate toxicity may require multiple glucarpidase administrations.
  • Glucarpidase efficacy can be influenced by factors leading to delayed drug clearance.
  • Aggressive supportive care is essential for mitigating methotrexate-induced kidney damage.

Implications:

  • Repeated glucarpidase dosing may be necessary for optimal methotrexate clearance in select patients.
  • Understanding factors contributing to delayed clearance is vital for refining treatment protocols.
  • This case series highlights the importance of integrated supportive measures in managing high-dose chemotherapy toxicity.

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