High‐dose methotrexate‐induced nephrotoxicity in patients with osteosarcoma
- 19 April 2004
- Vol. 100 (10), 2222-2232
- https://doi.org/10.1002/cncr.20255
Abstract
BACKGROUND High‐dose methotrexate (HDMTX)‐induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX‐induced nephrotoxicity has been managed with high‐dose leucovorin, dialysis‐based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase‐G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX‐induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis‐based methods of MTX removal with treatment using CPDG2. METHODS The literature was reviewed for osteosarcoma trials, use of dialysis‐based methods for MTX removal, and reports of MTX‐induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG2 and renal recovery after CPDG2 rescue was obtained from the database of a compassionate‐release trial. RESULTS Approximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade ≥ 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis‐based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG2. CPDG2 did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis‐based methods. CONCLUSIONS HDMTX‐induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG2 should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently. Cancer 2004. © 2004 American Cancer Society.Keywords
This publication has 82 references indexed in Scilit:
- Effective removal of methotrexate by high-flux hemodialysisPediatric Nephrology, 2002
- Effective clearance of methotrexate using high-flux hemodialysis membranesAmerican Journal of Kidney Diseases, 1996
- Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patientsEuropean Journal Of Cancer, 1994
- Charcoal Hemoperfusion and Methotrexate ToxicityNephron, 1991
- Survival After Unexpected High Serum Methotrexate Concentrations in a Patient with Osteogenic SarcomaDrug Safety, 1990
- Acute Renal Failure after High-Dose Methotrexate TherapyNephron, 1989
- Adriamycin-methotrexate high dose versus adriamycin-methotrexate moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized studyEuropean Journal of Cancer and Clinical Oncology, 1986
- The Effect of Adjuvant Chemotherapy on Relapse-Free Survival in Patients with Osteosarcoma of the ExtremityNew England Journal of Medicine, 1986
- Hemodialysis and enzymatic cleavage of methotrexate in manEuropean Journal of Cancer (1965), 1978
- Use of Plasma Pharmacokinetics to Predict and Prevent Methotrexate ToxicityNew England Journal of Medicine, 1977