Journal of Clinical Oncology, Vol 16, 1561-1567, Copyright © 1998 by American Society of Clinical Oncology
High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?
MJ Glantz, BF Cole, L Recht, W Akerley, P Mills, S Saris, F Hochberg, P Calabresi and MJ Egorin
Department of Medicine, Brown University School of Medicine, Providence, RI, USA. mjg@brownvm.brown.edu
PURPOSE: Standard treatments for neoplastic meningitis are only modestly
effective and are associated with significant morbidity. Isolated reports
suggest that concurrent systemic and intrathecal (i.t.) therapy may be more
effective than i.t. therapy alone. We present our experience, which
includes CSF and serum pharmacokinetic data, on the use of high-dose (HD)
intravenous (i.v.) methotrexate (MTX) as the sole treatment for neoplastic
meningitis. PATIENTS AND METHODS: Sixteen patients with solid-tumor
neoplastic meningitis received one to four courses (mean, 2.3 courses) of
HD (8 g/m2 over 4 hours) i.v. MTX and leucovorin rescue. Serum and CSF MTX
concentrations were measured daily. Toxicity, response, and survival were
retrospectively compared with a reference group of 15 patients treated with
standard i.t. MTX during the same time interval. RESULTS: Peak methotrexate
concentrations ranged from 3.7 to 55 micromol/L (mean, 17.1 micromol/L) in
CSF and 178 to 1,700 micromol/L (mean, 779 micromol/L) in serum. Cytotoxic
CSF and serum MTX concentrations were maintained much longer than with i.t.
dosing. Toxicity was minimal. Cytologic clearing was seen in 81% of
patients compared with 60% of patients treated intrathecally (P = .3).
Median survival in the HD i.v. MTX group was 13.8 months versus 2.3 months
in the i.t. MTX group (P = .003). CONCLUSION: HD i.v. MTX is easily
administered and well tolerated. This regimen achieves prolonged cytotoxic
serum MTX concentrations and CSF concentrations at least comparable to
those achieved with standard i.t. therapy. Cytologic clearing and survival
may be superior in patients treated with HD i.v. MTX. Prospective studies
and a reconsideration of the use of i.t. chemotherapy for patients with
neoplastic meningitis are warranted.
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