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Systemic
high dose methotrexate (HD MTX) for central nervous system (CNS) metastases
Andrew
B Lassman, Lauren E Abrey, Martin Begemann, Katherine J Picconi, Kelly Vuksanaj,
Mark G Malkin, Jeffrey J Raizer
Dept of
Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
Background.
Treatment options for patients with recurrent or progressive multiple CNS
metastases are limited.
Many patients also have active systemic disease requiring systemic treatment.
HD MTX has reasonable CNS penetration and activity against several malignant
neoplasms (Glantz MJ, et al. J Clin Oncol 1998; 16:1561-1567), especially breast
cancer.
Methods.
We report our experience using HD MTX (≥
3.5 g/m2) to treat patients with parenchymal and/or leptomeningeal CNS
metastases.
Survival, response patterns, and toxicities were compiled from
retrospective chart review.
Results.
We treated 21 patients (20 female and 1 male) with a median age of 51 years
(range 37 to 73).
19 patients had breast cancer and 1 each had a cancer of
unknown primary and a squamous cell carcinoma of the head and neck.
74 cycles of
HD MTX were administered to the 21 patients, with a mean of 3.5 cycles per
patient (range 1 to 9).
12 patients received low dose MTX previously for breast
cancer.
The median overall survival after the first dose of MTX was 3 months
(range 1 to 10+) with 5 patients still alive.
Radiographic and clinical response
rates are demonstrated in the table below.
We did not evaluate radiographic
response in patients treated with only 1 dose.
Acute renal failure, the most
serious toxicity, precluded further treatment in 2 (9.5%) patients.
Other
toxicities included: transient renal insufficiency in 8 (38%) patients, delayed
MTX clearance without a change in renal function in 2 (9.5%), hepatic
encephalopathy in 2 (9.5%), and symptomatic hyponatremia in 1 (4.8%).
Conclusion.
In these patients with recurrent or progressive CNS metastases, HD MTX has
activity and is generally well tolerated.
Although the median survival was only
3 months, more than half of our patients initially improved or
remained stable.
While some developed transient renal insufficiency, serious
toxicity was rare.
Prior treatment with MTX based regimens impacted neither
response nor toxicity.
|
Response
|
Radiographic
(n=14)
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Clinical
(n=21)
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Improved
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4
(29%)
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5
(24%)
|
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Stable
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7
(50%)
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7
(33%)
|
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Progressed
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3
(21%)
|
9
(43%)
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© Copyright 2002
American
Society of Clinical Oncology
Source:
http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-002083-00_29-00A-00_42-00ONeill-00_43-00-00_44-00-00_45-00
Author-00_46-00Title-00_47-00Title-00_48-00and-00_49-00and,00.asp?cat=CNS+Tumors&parent=CENTRAL+NERVOUS+SYSTEM+TUMORS
&returnpid=2323
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