Systemic high-dose intravenous methotrexate for central nervous system metastases

Andrew B. Lassman*, Lauren E. Abrey, Gaurav G. Shah, Katherine S. Panageas, Martin Begemann, Mark G. Malkin, Jeffrey J. Raizer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

102 Scopus citations


Background: Treatment options for patients with recurrent central nervous system (CNS) metastases are limited. Rapid infusion of high-dose intravenous methotrexate (HD IV MTX) penetrates the blood-brain barrier (BBB) and has reported activity in leptomeningeal metastases. Methods: Medical records were reviewed for all patients treated with HD IV MTX (3.5 g/m2) for CNS parenchymal or leptomeningeal metastases. Radiographic response rate, survival, and toxicity were determined. Results: Thirty-one women and one man with a median age of 52 years (range 33-76) were treated with a total of 141 cycles (median 4, range 1-13). Twenty-nine patients had breast cancer, and one each had cancer of unknown primary (CUP), squamous cell carcinoma of the head and neck, and non-small cell lung cancer (NSCLC). An objective radiographic response and stable disease were each observed in nine patients (28%), and 13 (44%) patients progressed. Prior treatment with low-dose MTX for systemic disease did not affect response (P = 0.8). The median overall survival (n = 32) was 19.9 weeks (range 2.9-135.4+) with one patient alive at 135.4 weeks. Myelosuppression and elevated serum hepatic transaminases were the most common acute toxicities (21% and 9% of HD IV MTX cycles, respectively). Conclusions: HD IV MTX is effective in the treatment of CNS metastases with disease control (response or stable) as a best response in 56% of assessable patients. Further study is warranted.

Original languageEnglish (US)
Pages (from-to)255-260
Number of pages6
JournalJournal of Neuro-Oncology
Issue number3
StatePublished - Jul 2006


  • Brain
  • Central nervous system
  • Chemotherapy
  • Leptomeninges
  • Metastases
  • Methotrexate

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research


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