High-Dose Methotrexate Therapy (6‐8 G/M²) in Childhood Malignancies: Clinical Tolerability and Pharmacokinetics

Abstract

Five children, ages 2.5 to 12 years (mean 6.2 years), with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were given 22 courses of high-dose methotrexate (HD-MTX) therapy (6–8 g/m²/24 h). No serious clinical complications were encountered, but stomatitis occurred after three (14%) of the courses. First-phase elimination half-lives (t_1/2(α)) of MTX and 7-hydroxy-methotrexate(7-OH-MTX) after 21 infusions were 2.7 ± 0.4 hand 6.5 ± 1.8 h (mean ± SD). In one course (4.5%) there was delayed systemic MTX elimination, with first-phase elimination half-lives (t_1/2(α)) for MTX and 7-OH-MTX of 4.2 and 9.9 h, respectively, and second-phase elimination half-lives (t_1/2(β)) of 43 and 58 h. Significant decreases in white blood cell count, increases in serum creatinine, and increases in alanine aminotransferase and/or aspartate aminotransferase during the first 2–6 days were present in five (23%), three (14%), and six (27%) of the courses, respectively. The regimen was tolerated well by the children.

Key Words:

• methotrexate
• 7-hydroxy-methotrexate
• toxicity
• pharmacokinetics