Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions: A prospectively randomized cross-over study

Abstract

Alkalized hydration is used as supportive care to prevent renal toxicity during infusions with high-dose methotrexate (HDMTX). In children with acute lymphoblastic leukemia (ALL), the hydration is commonly initiated 4 hours before start of the methotrexate (MTX) infusion. To test if longer duration of prehydration would prevent MTX-induced renal toxicity, we preformed a randomized cross-over study comparing 12-4 hours of hydration before the infusion of HDMTX. Children with ALL and non-Hodgkin lymphoma that were treated with infusions of HDMTX 5 or 8 g/m(2) were randomized to receive intravenous prehydration 12 or 4 hours before the first HDMTX infusion. Patients alternated between 12 and 4 hours of prehydration in the subsequent HDMTX infusions. Renal toxicity was defined as 50% increase in plasma creatinine after the HDMTX infusion. The plasma MTX concentration was measured during and after the HDMTX infusion to determine if the duration of prehydration would influence the systemic MTX clearance. A total of 47 patients (224 HDMTX infusions) with a median age of 4.9 years were included in the study. The duration of prehydration had no effect on MTX induced renal toxicity that occurred in 18.5% of all HDMTX 5 g/m(2) infusions and in 40.0% of all HDMTX 8 g/m(2) infusions. Similar the duration of prehydration had no impact on the systemic clearance of MTX. Extending prehydration beyond 4 hours does not reduce the risk of renal toxicity or delayed MTX clearance after infusions with HDMTX 5-8 g/m(2).