EPT-03
PHARMACOKINETICS OF HIGH-DOSE METHOTREXATE IN INFANTS AGED LESS THAN 12 MONTHS TREATED FOR BRAIN TUMORS

In infants aged less than 12 months there are few data on pharmacokinetics of high-dose methotrexate (HD-MTX) for brain tumors at the dose of 8 g/m2. Consolidated knowledge are present only with the dose of 5 g/m2 in acute lymphoblastic leukemia. We collected data on 8 infants at the time of their first treatment with HD-MTX, 8 g/m2. All children had a dose adjustment with a weight-based prescription (1 m2 = 30 Kg). The median age was 4,5 months (range 0-9). The median weight was 5,63 kg (range 3,12-9,0). The median steady-state MTX concentration at the end of 6-hr infusion was 486 µM/L (range 227-790). The median systemic MTX-clearance was 4,14 L/hr/m2 (range 1,98-9,35). The median MTX concentration after 24-hr from the beginning of infusion was 3,29 µM/L (range 1,14-100,44). Three (37,5%) patients had a delayed elimination of MTX (delayed early, delayed late, or total delayed: one for each). These altered elimination occurred principally in children weighing less than 4 kg (p: 0.0179). Moreover, a systemic MTX-clearance at the end of infusion minor than 3 L/hr/m2 can predict a delayed elimination (p: 0.0179). Patients with altered elimination underwent to rescue measures (leucovorin supplement and/or exchange transfusion). Our data suggest that an higher dose of HD-MTX for the treatment of brain tumors had an acceptable pharmacokinetic profile. Greater attention must be used in the treatment of children weighing less than 4 kg.