High-dose methotrexate therapy (6-8 g/m2) in childhood malignancies: clinical tolerability and pharmacokinetics.
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.
Slørdal
L
L
Department of Pharmacology, University of Tromsø, Norway.
Kolmannskog
S
S
Moe
P J
PJ
Prytz
P S
PS
Aarbakke
J
J
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004341:Drug Evaluation; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy*; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D013280:Stomatitis / Q000139:chemically induced; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate