Journal of Neuro-Oncology

, Volume 78, Issue 3, pp 255–260 | Cite as

Systemic high-dose intravenous methotrexate for central nervous system metastases

  • Andrew B. LassmanEmail author
  • Lauren E. Abrey
  • Gaurav G. Shah
  • Katherine S. Panageas
  • Martin Begemann
  • Mark G. Malkin
  • Jeffrey J. Raizer
Clinical-patient studies



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.


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.


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).


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.


brain central nervous system chemotherapy leptomeninges metastases methotrexate 


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Judy Lampron and Bill Carey provided key editorial and administrative assistance. Katherine Picconi and Kelly Vuksanaj cared for the majority of patients involved in this study, and we are indebted to them and to our other Neurology Nurse Practitioners. Preliminary results were presented at the 2002 American Society of Clinical Oncology and Society for Neuro-Oncology annual meetings.

This work was supported in part by the American Brain Tumor Association and grant number CA009512 from the National Cancer Institute.


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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Andrew B. Lassman
    • 1
    • 5
    Email author
  • Lauren E. Abrey
    • 1
  • Gaurav G. Shah
    • 1
  • Katherine S. Panageas
    • 2
  • Martin Begemann
    • 3
  • Mark G. Malkin
    • 4
  • Jeffrey J. Raizer
    • 5
  1. 1.Departments of NeurologyMemorial Sloan-Kettering Cancer Center New YorkUSA
  2. 2.Epidemiology, Biostatistics, Memorial Sloan-Kettering Cancer Center New YorkUSA
  3. 3.Department of NeurologyMax Planck Institute for Molecular Genetics BerlinGermany
  4. 4.Department of NeurologyMedical College of WisconsinMilwaukeeUSA
  5. 5.Department of NeurologyNorthwestern University, Feinberg School of Medicine and Robert H. Lurie Cancer CenterChicagoUSA

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