Prolonged methotrexate infusions in children with acute leukemia in relapse and in remission and with medulloblastoma. Pharmacokinetics, toxicity and clinical results.

Abstract:

:In 86 children with acute lymphocytic leukemia (ALL) and in 6 children with medulloblastoma 253 24-hour methotrexate (MTX) infusions with 150, 500, and 700 mg/m2 were performed. MTX concentrations in plasma and cerebrospinal fluid (CSF) were measured with a specific radioimmunoassay. In 131 infusions with 500 mg/m2 given to patients with ALL in remission, the MTX plasma concentration 24 h after the end of infusion did not exceed 7 X 10(-7) mol/1. Mild hematologic toxicity occurred in 22% of the treatment cycles. In contrast 8/45 infusions given to patients with ALL in relapse were associated with delayed MTX elimination followed by severe toxicity. The CSF: plasma ratio of MTX measured during 58 infusions did not exceed 11% in patients with ALL in remission, but was above this value in 13/34 infusions in patients with leukemia of the central nervous system (CNS). 24-hour MTX infusions with 500 mg/m2 were as hepatotoxic as 4- to 6-hour infusions with 3-8.5 g/m2. With MTX as single agent no remissions were achieved in 8 patients with ALL in relapse. The addition of asparaginase in 10 patients resulted in 3 complete and 2 partial remissions. In patients with ALL in first remission clinical results confirmed the value of intensive MTX therapy for disease-free survival.

journal_name

Oncology

journal_title

Oncology

authors

Janka GE,Mack R,Helmig M,Haas RJ,Bidlingmaier F

doi

10.1159/000225828

subject

Has Abstract

pub_date

1984-01-01 00:00:00

pages

225-32

issue

4

eissn

0030-2414

issn

1423-0232

journal_volume

41

pub_type

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