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  • Title: High-dose methotrexate therapy (6-8 g/m2) in childhood malignancies: clinical tolerability and pharmacokinetics.
    Author: Slørdal L, Kolmannskog S, Moe PJ, Prytz PS, Aarbakke J.
    Journal: Pediatr Hematol Oncol; 1987; 4(1):33-42. PubMed ID: 3152911.
    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 (t1/2(alpha)) of MTX and 7-hydroxy-methotrexate (7-OH-MTX) after 21 infusions were 2.7 +/- 0.4 h and 6.5 +/- 1.8 h (mean +/- SD). In one course (4.5%) there was delayed systemic MTX elimination, with first-phase elimination half-lives (t1/2(alpha] for MTX and 7-OH-MTX of 4.2 and 9.9 h, respectively, and second-phase elimination half-lives (t1/2(beta)) 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.
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