CORRESPONDENCE
Letter: When Less is More: Dexamethasone
Dosing for Brain Tumors
To the Editor:
We are writing to highlight the discrepancy in dosing schedules
for corticosteroids used to treat peritumoral edema between the
neurosurgical community and the neuro-oncology community
and suggest that it may be time to re-evaluate the dosing of dexam-
ethasone for brain tumors.
Corticosteroids have been ubiquitously used to treat brain
tumor patients with cerebral edema since the 1950s. In particular,
dexamethasone, due to its low mineralocorticoid potency and
high glucocorticoid activity, is arguably the most commonly used
symptomatic agent out of the limited armamentarium available
to physicians caring for brain tumor patients. This widespread
practice traces its origin in part to the landmark paper by Dr
Joseph Galicich and colleagues from the University of Minnesota
in 1961.1 In this study, 14 patients with brain tumor-related
cerebral edema were treated with an initial bolus of 10 to 40 mg
of dexamethasone, followed by a regimen of 4 mg intramuscularly
every 6 h. A total of 13 out of the 14 patients experienced a signif-
icant improvement in their neurological symptoms, and dexam-
ethasone was hence deemed a “safe and highly effective” agent in
the treatment of tumor-related cerebral edema. Since that time, it
has been standard practice for dexamethasone to be administered
to patients every 6 h, including, frequently, in the middle of the
night.
While the benefit of dexamethasone can be dramatic both
clinically and radiographically, particularly in patients with
brain metastases and lymphoma, balancing the side effects
remains a real challenge, and overuse of dexamethasone is
common. Steroid-related toxicities present a significant concern
over time and include iatrogenic Cushing’s syndrome, behav-
ioral issues, myopathy, opportunistic infections, and osteo-
porosis. In addition, early steroid use in primary brain
tumor patients has been associated with increased morbidity
and mortality.2 As newer therapies attempt to augment the
immune response in the treatment of brain tumors, the use of
steroids for symptomatic relief has become counterproductive
in many cases. Every attempt should be made to start at the
lowest effective dose and taper as rapidly and as safely as
possible.
Dosage and tapering of dexamethasone in brain tumor-related
cerebral edema are physician, specialty, institution, and patient
dependent. Over time, there has been a growing discrepancy
between the dose and schedule of dexamethasone used by the
neurosurgical and the neuro-oncology communities. Most neuro-
surgeons initiate dexamethasone at 4 mg every 6 h, following
a bolus, and maintain an every 6 h schedule for lower doses.
In contrast, most neuro-oncologists administer dexamethasone
twice daily or even once daily. These schedules are significantly
NEUROSURGERY
easier for patients and have not been associated with diminished
efficacy.
Dexamethasone has a biological half-life of 36 to 54 h (despite
a plasma half-life of about 4 hs) and can provide a symptomatic
benefit for a prolonged duration.3 A study published in 1990,
which utilized autoradiography to monitor capillary permeability
to study peritumoral edema in a C6 rat glioma model, revealed
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that a single dose of dexamethasone maintained a reduction
in capillary permeability over a 12-h course.4 Another study
corroborated a substantial reduction in vascular permeability and
water content of tumor and peritumoral brain tissue in RG2 rat
glioma following twice daily dexamethasone dosing.5 Although
rigorous patient studies on twice per day dexamethasone dosing
are lacking, a small pilot study of 14 patients with intracranial
metastases on a twice daily tapering regimen starting at 8 mg twice
a day showed similar rates of clinical response and no neurological
decline when compared to historical cohorts.6
Administering corticosteroids every 6 h frequently can result
in poor sleep due to medication-related effects or medication
administration itself, contributing to increased daytime fatigue.
In a population where preserving the quality of life is paramount,
and in the absence of evidence to justify more frequent dosing,
we hope the neurosurgical community will join the neuro-
oncology community and consider changing its practice to
once or twice a day dosing of dexamethasone for brain tumor
patients.
Disclosures
Dr Colman is on the Advisory Board for and is a consultant for Abbvie,
Foundation Medicine, Innocrin, Tactical Therapeutics, Deciphera, Newlink
Genetics, Best Doctors, Merck, and Karyopharm Therapeutics, and receives
research funding (Site PI/Institutional Contract): Newlink Genetics, Plexxikon,
Kadmon, Orbus, Merck, DNATrix, Abbvie, Beigene, and Forma. Dr Lo is on
the Advisory Board for Gilead Sciences and is a consultant for Viiv Healthcare.
Dr Mellinghoff receives research funding from General Electric, Amgen, and
Lilly, has advisory roles with Agios, Puma Biotechnology, and Debiopharm
Group, and has received honoraria from Roche for a presentation. Dr Mehta is
a consultant for Varian, Abbvie, Celgene, Astra-Zeneca, Tocagen, and Blue Earth
Diagnostics, and is on the Board of Directors for Oncoceutics. Dr Lassman has
received honoraria/travel/research support (prior 12 mo, all outside the submitted
work) from Karyopharm, NW Bio, Agios, AbbVie, Sapience, Oncoceutics,
Novocure, Tocagen, Genentech/Roche, Amgen, Millenium, Celldex, Novartis,
Pfizer, Aeterna Zentaris, Pfizer, Kadmon, VBI Vaccines, Beigene, and Bioclinica.
Dr Ahluwalia has received grants/research support from Astrazeneca, Abbvie,
BMS, Bayer, Incyte, Pharmacyclics, Novocure, and Merck, has received honoraria
or consultation fees from Elsevier, Wiley, Astrazeneca, Abvvie, VBI Vaccines,
Flatiron, Varian Medical Systems, and Prime Education, and is a stock shareholder
in Doctible and Mimiva.
Mary Jane Lim-Fat, MD∗
Wenya Linda Bi, MD, PhD‡
Janet Lo, MD§
VOLUME 85 | NUMBER 3 | SEPTEMBER 2019 | E607
CORRESPONDENCE
Eudocia Quant Lee, MD, MPH∗ ¶
Manmeet S. Ahluwalia, MD||
Tracy T. Batchelor, MD, MPH∗ ¶
Susan M. Chang, MD#
E. Antonio Chiocca, MD, PhD‡
Ugonma Chukwueke, MD∗ ¶
Timothy F. Cloughesy, MD∗∗
Howard Colman, MD, PhD‡‡
Lisa M. Deangelis, MD§§
Evanthia Galanis, MD¶¶
Mark R. Gilbert, MD||||
John F. De Groot, MD##
Andrew B. Lassman, MD∗∗∗
Linda M. Liau, MD, PhD, MBA‡‡‡
Warren Mason, MD§§§
J. Ricardo McFaline-Figueroa, MD, PhD∗ ¶
Minesh P. Mehta, MD¶¶¶
Ingo K. Mellinghoff, MD§§
L. Burt Nabors, MD||||||
Lakshmi Nayak, MD∗ ¶
David A. Reardon, MD∗ ¶
Patrick Y. Wen, MD∗ ¶
∗
Center for Neuro-Oncology
Dana Farber Cancer Institute
Boston, Massachusetts
‡
Department of Neurosurgery
Brigham and Women’s Hospital
Boston, Massachusetts
§
Neuroendocrine Unit
Massachusetts General Hospital
Boston, Massachusetts
¶
Department of Neurology
Brigham and Women’s Hospital
Boston, Massachusetts
||
Burkhardt Brain Tumor and Neuro-Oncology Center
Cleveland Clinic
Cleveland, Ohio
# 4. Shapiro WR, Hiesiger EM, Cooney GA, Basler GA, Lipschutz LE, Posner JB.
Department of Neurological Surgery
University of California, San Francisco
San Francisco, California
∗∗
UCLA Neuro-Oncology Program
University of California, Los Angeles
Los Angeles, California
‡‡
Huntsman Cancer Institute and Department of Neurosurgery
University of Utah
Salt Lake City, Utah
E608 | VOLUME 85 | NUMBER 3 | SEPTEMBER 2019
§§
Department of Neurology
Memorial Sloan Kettering Cancer Center
New York, New York
¶¶
Division of Medical Oncology
Mayo Clinic
Rochester, Minnesota
||||
Neuro-Oncology Branch
Center for Cancer Research
National Cancer Institute
Bethesda, Maryland
Downloaded from https://academic.oup.com/neurosurgery/article/85/3/E607/5520500 by guest on 26 November 2021
##
Department of Neuro-Oncology
The University of Texas M.D. Anderson Cancer Center
Houston, Texas
∗∗∗
Division of Neuro-Oncology
Department of Neurology, and Herbert Irving Comprehensive
Cancer Center
Columbia University Irving Medical Center
New York-Presbyterian Hospital
New York, New York
‡‡‡
Department of Neurosurgery
University of California, Los Angeles
Los Angeles, California
§§§
Division of Neurology
Princess Margaret Hospital, Toronto
Ontario, Canada
¶¶¶
Department of Radiation Oncology
Miami Cancer Institute
Coral Gables, Florida
||||||
UAB Comprehensive Cancer Center
The University of Alabama at Birmingham
Birmingham, Alabama
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10.1093/neuros/nyz186
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