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.
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 creatininetoxicity 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.
Authors: Marc Ghannoum; Darren M Roberts; David S Goldfarb; Jesper Heldrup; Kurt Anseeuw; Tais F Galvao; Thomas D Nolin; Robert S Hoffman; Valery Lavergne; Paul Meyers; Sophie Gosselin; Tudor Botnaru; Karine Mardini; David M Wood Journal: Clin J Am Soc Nephrol Date: 2022-03-02 Impact factor: 10.614
Authors: John R Carr; W Anthony Hawkins; Andrea Sikora Newsome; Susan E Smith; Clemmons Amber B; Christopher M Bland; Trisha N Branan Journal: J Pharm Pract Date: 2021-04-08
Authors: Laura B Ramsey; Frank M Balis; Maureen M O'Brien; Kjeld Schmiegelow; Jennifer L Pauley; Archie Bleyer; Brigitte C Widemann; David Askenazi; Sharon Bergeron; Anushree Shirali; Stefan Schwartz; Alexander A Vinks; Jesper Heldrup Journal: Oncologist Date: 2017-10-27