Serum and Cerebrospinal Fluid Distribution of 5-Methyltetrahydrofolate after Intravenous Calcium Leucovorin and Intra-Ommaya Methotrexate Administration in Patients with Meningea! Carcinomatosis1

Serum and cerebrospinal fluid (CSF) concentrations of citrovorum factor (CF) and 5-methyltetrahydrofolic acid (5MTHFA) were measured after i.v. infusion of leucovorin (50 or 100 mg/sq m) in seven patients undergoing treatment for meningeal carcinomatosis by intra-Ommaya reservoir injection of methotrexate (MIX). Serum CF levels rapidly rose after leucovorin administration as did 5-MTHFA, its conversion prod uct. A small amount of CF entered the CSF, but peak CSF 5MTHFA increased about 10-fold. The concentration x time (C x 0 of additional 5-MTHFA in the CSF was greater [114.4 ± 36.1 (S.E.) jug/ml x min] after 100-mg/sq m doses of leuco vorin than after 50 mg/sq m [14.2 ±4.3 /ig/ml x min] (p < 0.05). The CSF MTX concentration exceeded CSF 5-MTHFA by 2 to 3 logs throughout the 48 hr of observation, while serum 5-MTHFA and CF exceeded serum MTX by 0.5 to 2 logs. This study demonstrates that leucovorin administered i.v. to patients receiving intra-Ommaya MTX does not increase CSF concen trations of "rescue" folate above those of CSF MTX and are unlikely to interfere with MTX action against meningeal tumor. On the other hand, i.v. leucovorin does permit serum "rescue" folate to operate, thus reducing the systemic toxicity that may follow intraventricular administration of MTX.