HIGH-DOSE INTRAVENOUS METHOTREXATE FOR PATIENTS WITH NONLEUKEMIC LEPTOMENINGEAL CANCER - IS INTRATHECAL CHEMOTHERAPY NECESSARY

Purpose: Standard treatments for neoplastic meningitis are only modest ly effective and are associated with significant morbidity, Isolated r eports suggest that concurrent systemic and intrathecal (IT) therapy m ay be more effective than IT therapy alone. We present our experience, which includes CSF and serum pharmacokinetic data, on the use of high -dose (HD) intravenous (IV) methotrexate (MTX) as the sole treatment f or 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/m(2) over 4 hours) IV MTX and leucovorin rescu e. Serum and CSF MTX concentrations were measured daily. Toxicity, res ponse, and survival were retrospectively compared with a reference gro up of 15 patients treated with standard IT MTX during the same time in terval. Results: Peak methotrexate concentrations ranged from 3.7 to 5 5 mu mol/L (mean, 17.1 mu mol/L) in CSF and 178 to 1,700 mu mol/L (mea n, 779 mu mol/L) in serum, Cytotoxic CSF and serum MTX concentrations were maintained much longer than with IT dosing. Toxicity was minimal, Cytologic clearing was seen in 81% of patients compared with 60% of p atients treated intrathecally (P = .3). Median survival in the HD IV M TX group was 13.8 months versus 2.3 months in the IT MTX group (P = .0 03). Conclusion: HD IV 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 standar d IT therapy. Cytologic clearing and survival may be superior in patie nts treated with HD IV MTX. Prospective studies and a reconsideration of the use of IT chemotherapy for patients with neoplastic meningitis are warranted. (C) 1998 by American Society of Clinical Oncology.