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Related Experiment Videos

Understanding and managing methotrexate nephrotoxicity.

Brigitte C Widemann1, Peter C Adamson

  • 1Pediatric Oncology Branch, National Cancer Institute, 10 Center Drive, Building 10 CRC Room 1-5750, Bethesda, Maryland 20892-1101, USA. widemanb@mail.nih.gov

The Oncologist
|June 24, 2006
PubMed
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High-dose methotrexate (HDMTX) can cause kidney problems. Carboxypeptidase-G(2) (CPDG(2)) effectively and rapidly reduces MTX levels in patients with HDMTX-induced renal dysfunction.

Area of Science:

  • Oncology
  • Pharmacology
  • Nephrology

Background:

  • High-dose methotrexate (HDMTX) is a critical chemotherapy agent for various cancers.
  • HDMTX administration requires careful monitoring and supportive care, including leucovorin (LV) rescue, hydration, and alkalinization, to mitigate toxicity in patients with normal renal function.
  • Despite these measures, HDMTX-induced renal dysfunction occurs in approximately 1.8% of patients, necessitating prompt recognition and management to prevent severe toxicities like myelosuppression, mucositis, and dermatitis.

Purpose of the Study:

  • To evaluate the efficacy and safety of carboxypeptidase-G(2) (CPDG(2)) in managing HDMTX-induced renal dysfunction.
  • To assess the impact of CPDG(2) on plasma MTX concentrations in patients experiencing renal complications.
  • To determine the potential benefits of early CPDG(2) administration in conjunction with LV rescue.

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Main Methods:

  • Review of clinical data for patients treated with HDMTX and subsequent renal dysfunction.
  • Administration of recombinant bacterial enzyme carboxypeptidase-G(2) (CPDG(2)) to hydrolyze MTX.
  • Monitoring of plasma MTX concentrations before and after CPDG(2) administration.
  • Assessment of patient tolerance to CPDG(2) treatment.

Main Results:

  • CPDG(2) administration was well-tolerated by patients.
  • CPDG(2) resulted in consistent and rapid reductions in plasma MTX concentrations, with a median reduction of 98.7% (range, 84%-99.5%).
  • Dialysis methods have shown limited effectiveness in removing MTX.

Conclusions:

  • CPDG(2) is an effective therapeutic option for managing HDMTX-induced renal dysfunction.
  • Early intervention with CPDG(2) alongside LV rescue may be beneficial for patients with significantly elevated plasma MTX levels.
  • CPDG(2) offers a promising approach to mitigate MTX-associated toxicities by rapidly lowering drug concentrations.