Study to Determine the Maximum Tolerated Time of Infusion for High-Dose Methotrexate, Administered as a Continuous Intravenous Infusion at a Dose of 6g/m² Per 24 Hours of Infusion Time
- To determine the maximum tolerated time to exposure to high-dose methotrexate when
administered as a continuous infusion at a dose of 6 g/m² per 24 hours.
- To relate the methotrexate schedules investigated to the magnitude and duration of
changes in plasma homocysteine and methionine.
- To relate evidence of the systemic effect of methotrexate through changes in plasma
homocysteine and methionine to any hepatic, neurological, or antiproliferative toxicity
observed in the study group.
OUTLINE: Patients receive a continuous infusion of high-dose methotrexate IV over 24, 30,
36, or 42 hours depending on time of study entry. Beginning at hour 42 or 48, patients
receive leucovorin calcium IV every 6 hours for 3 days or until plasma methotrexate
concentration is < 0.2 µM. Treatment repeats every 2 weeks in the absence of disease
progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study and analyzed for
pharmacodynamic effects on plasma homocysteine and methionine by gas chromatography/mass
Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated infusion time for high-dose methotrexate
Eddy J. Estlin
Royal Manchester Children's Hospital
United States: Federal Government