Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma

Abstract

Purpose: To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyper-hydration.

Methods: Patients with osteosarcoma received HDMTX (8-12 g/m(2)) as a 4-h infusion. Hypertonic 8.4% sodium bicarbonate was infused prior to HDMTX, then once daily for 3 days. Methotrexate serum concentrations were measured at hour 4 (Cmax), hour 24, hour 48, and hour 72. Urinary pH was measured on each miction. Serum creatinine was assessed on days 1, 3, and 8.

Results: Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344 cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH remained constantly higher than 7.5 in all patients. Grade 1 creatininemia toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was observed in one patient. No episode of acute severe nephrotoxicity was observed. No significant worsening was observed in serum creatinine and calculated creatinine clearance from baseline to the end of therapy (P = 0.74). The main extra-renal toxicity was alkalinization-related hypokalemia from H48. No re-hospitalization was required.

Conclusion: Hyper-alkalinization appears an efficient and reliable method to prevent the acute renal toxicity of HDMTX and allows its safe administration in the outpatient setting.