Renal dysfunction during and after high-dose methotrexate.

Area of Science:

• Oncology
• Nephrology
• Pharmacology

Background:

• Primary central nervous system lymphoma (PCNSL) is a rare but aggressive malignancy.
• High-dose methotrexate (HDMTX) is a cornerstone treatment for PCNSL.
• Renal toxicity is a known complication of HDMTX therapy.

Purpose of the Study:

• To evaluate the incidence and severity of renal dysfunction in adult PCNSL patients receiving repeated HDMTX cycles.
• To identify risk factors associated with HDMTX-induced renal impairment.

Main Methods:

• Retrospective analysis of 23 adult PCNSL patients treated with at least four cycles of HDMTX (8 gm/m(2)/dose).
• Monitoring of serum creatinine and serum methotrexate levels at 24, 48, and 72 hours post-infusion.
• Assessment of renal dysfunction using NCI Common Toxicity Criteria (CTC) and evaluation for glucarpidase administration.

Main Results:

• 48% of patients experienced a >or=200% increase in baseline creatinine; 30% of HDMTX cycles showed this increase.
• 9% of patients required glucarpidase (carboxypeptidase-G(2)) administration.
• 30% of patients had CTC grade 2 or higher increase in post-treatment serum creatinine, with 43% of these having abnormal levels.

Conclusions:

• Renal dysfunction (CTC grade 2-4) is common during HDMTX treatment for PCNSL, occurring in 40% of cycles.
• Renal impairment can persist for at least 4 months post-therapy in nearly 30% of patients.
• Male patients over 50 years old are at the highest risk for developing renal dysfunction.