Systemic high-dose intravenous methotrexate for central nervous system metastases.
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.
Lassman
Andrew B
AB
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Lassmana@mskcc.org
Abrey
Lauren E
LE
Shah
Gaurav D
GD
Shah
Gaurav G
GG
Panageas
Katherine S
KS
Begemann
Martin
M
Malkin
Mark G
MG
Raizer
Jeffrey J
JJ
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate