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High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma
Brigitte C Widemann1, Frank M Balis, Beate Kempf-Bielack
1Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1920, USA. bw42y@nih.gov
Cancer
|May 13, 2004
Summary
High-dose methotrexate (HDMTX) can cause kidney problems in osteosarcoma patients. Carboxypeptidase-G2 (CPDG2) effectively removes MTX, offering a better alternative to dialysis for managing this toxicity.
Area of Science:
- Oncology
- Pharmacology
- Nephrology
Background:
- High-dose methotrexate (HDMTX) can cause life-threatening renal dysfunction by delaying methotrexate (MTX) excretion.
- Management strategies include leucovorin, dialysis, thymidine, and carboxypeptidase-G2 (CPDG2).
- CPDG2 is an enzyme that cleaves MTX into inactive metabolites.
Purpose of the Study:
- To estimate the incidence of HDMTX-induced renal dysfunction in osteosarcoma patients.
- To compare the efficacy of dialysis-based MTX removal with CPDG2 treatment.
- To assess renal function recovery in both treatment groups.
Main Methods:
- Literature review of osteosarcoma trials and MTX removal methods.
- Analysis of clinical trial databases for osteosarcoma studies.
- Review of compassionate-release trial data for CPDG2 efficacy and renal recovery.
Main Results:
- Approximately 1.8% of osteosarcoma patients receiving HDMTX developed Grade ≥2 nephrotoxicity.
- Mortality rate in affected patients was 4.4%.
- CPDG2 achieved rapid >98% reduction in plasma MTX concentrations, outperforming dialysis; renal recovery was comparable.
Conclusions:
- HDMTX-induced renal dysfunction remains a concern in osteosarcoma treatment (approx. 1.8% incidence).
- CPDG2 is a more rapid and efficient option than hemodialysis for reducing high plasma MTX concentrations.
- CPDG2 should be considered for patients with delayed MTX excretion and elevated MTX levels.