Renal dysfunction during and after high-dose methotrexate

To evaluate renal dysfunction in adult patients encountered during and immediately after repeated administrations of high-dose methotrexate (HDMTX) for treatment of primary central nervous system lymphoma (PCNSL).

In this single-center, retrospective, open label trial, 23 consecutive adult patients aged between 19 and 94 years diagnosed with PCNSL were given >or=4 consecutive cycles of HDMTX (8 gm/m(2)/dose) every 14 days as per institution protocol. Serum creatinine and serum methotrexate levels were measured at 24, 48 and 72 h after beginning of HDMTX infusion.

Forty-eight percent of all patients (30% of all HDMTX cycles) experienced a >or=200% increase in baseline creatinine during treatment. Nine percent of patients met requirements for administration of carboxypeptidase-G(2) (glucarpidase) under compassionate use from National Cancer Institute. Thirty percent of patients at the conclusion of HDMTX therapy demonstrated a NCI Common Toxicity Criteria (CTC) grade 2 or higher increase in post-treatment serum creatinine compared to pre-treatment serum creatinine amongst whom ten patients (43%) had levels outside of the normal range.

Renal dysfunction of CTC grade 2, 3 or 4 is common during treatment with HDMTX in the treatment of PCNSL, occurring in 40% of all cycles. Renal dysfunction persists at least 4 months following the conclusion of therapy in nearly 30% of patients. Male patients age greater than 50 years are at greatest risk of renal dysfunction.