Understanding and managing methotrexate nephrotoxicity

Brigitte C. Widemann, Peter C. Adamson

Research output: Contribution to journalArticle

Abstract

Methotrexate (MTX) is one of the most widely used anticancer agents, and administration of high-dose methotrexate (HDMTX) followed by leucovorin (LV) rescue is an important component in the treatment of a variety of childhood and adult cancers. HDMTX can be safely administered to patients with normal renal function by the use of alkalinization, hydration, and pharmacokinetically guided LV rescue. Despite these measures, HDMTX-induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma treated on clinical trials. Prompt recognition and treatment of MTX-induced renal dysfunction are essential to prevent potentially life-threatening MTX-associated toxicities, especially myelosuppression, mucositis, and dermatitis. In addition to conventional treatment approaches, dialysis-based methods have been used to remove MTX with limited effectiveness. More recently carboxypeptidase-G 2 (CPDG2), a recombinant bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites, has become available for the treatment of HDMTX-induced renal dysfunction. CPDG2 administration has been well tolerated and resulted in consistent and rapid reductions in plasma MTX concentrations by a median of 98.7% (range, 84%-99.5%). The early administration of CPDG2 in addition to LV may be beneficial for patients with MTX-induced renal dysfunction and significantly elevated plasma MTX concentrations.

Original languageEnglish (US)
Pages (from-to)694-703
Number of pages10
JournalOncologist
Volume11
Issue number6
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Methotrexate
gamma-Glutamyl Hydrolase
Leucovorin
Kidney
Mucositis
Dermatitis
Osteosarcoma
Therapeutics
Antineoplastic Agents
Dialysis
Clinical Trials

Keywords

  • Carboxypeptidase-G
  • Hemodialysis Hemoperfusion
  • High-dose chemotherapy
  • Methotrexate toxicity
  • Renal dysfunction
  • Rescue agents
  • Thymidine

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

Understanding and managing methotrexate nephrotoxicity. / Widemann, Brigitte C.; Adamson, Peter C.

In: Oncologist, Vol. 11, No. 6, 2006, p. 694-703.

Research output: Contribution to journalArticle

Widemann, Brigitte C. ; Adamson, Peter C. / Understanding and managing methotrexate nephrotoxicity. In: Oncologist. 2006 ; Vol. 11, No. 6. pp. 694-703.
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