An Evidence-Based Summary of Recommendations for the use of Dexamethasone in the Management of Brain Metastases

Special Article - Palliative Care

J Fam Med. 2016; 3(1): 1047.

An Evidence-Based Summary of Recommendations for the use of Dexamethasone in the Management of Brain Metastases

Vijayaratnam N¹, Gagnon L², Kwan R², Leguerrier B³, Huang F³ and Fairchild A1,3*

¹Faculty of Medicine, University of Alberta, Canada

²Department of Pharmacy, Cross Cancer Institute, Canada

³Palliative Radiation Oncology Program, Department of Radiation Oncology, Cross Cancer Institute, Canada

*Corresponding author: Fairchild A, Department of Radiation Oncology, Cross Cancer Institute, 11560 University Ave, Canada

Received: December 03, 2015; Accepted: January 11, 2016; Published: January 13, 2016


Intracranial edema associated with brain metastases commonly contributes to symptoms of headache, nausea or emesis. Corticosteroids are the pharmacologic agent of choice for many patients, to temporize symptoms until definitive antineoplastic therapy can be initiated. However, careful management is required to minimize related side effects which may compromise a patient’s quality of life. The literature on dosing, appropriate duration of therapy and tapering will be reviewed, along with practical guidelines on the initiation of dexamethasone, appropriate prophylaxis, and secondary screening for adverse events.

Keywords: Brain metastases; Dexamethasone; Steroid; Taper; Radiotherapy; Palliative


AVN: Avascular Necrosis; BID: Twice Daily; BBB: Blood- Brain Barrier; CT: Computed Tomography; CVA: Cerebrovascular Accident; DM: Diabetes Mellitus; DXM: Dexamethasone; GERD: Gastroesophageal Reflux Disease; GI: Gastrointestinal; ICP: Intracranial Pressure; MRI: Magnetic Resonance Imaging; NR: Not Reported; nSAID: non-Steroidal Anti-Inflammatory; OD: Daily; PCP: Pneumocystis Carinii Pneumonia; PE: Pulmonary Embolus; PJP: Pneumocystis Jurovecii Pneumonia; QID: Four Times Daily; RCC: Renal Cell Carcinoma; RCT: Randomized Controlled Trial; RT: Radiotherapy; TB: Tuberculosis; VTE: Venous Thromboembolism; WBRT: Whole Brain Radiotherapy


Almost 10% of all patients with cancer will develop brain metastases, which are most commonly diagnosed in lung, renal, breast, and colorectal cancers, and melanoma [1,2]. The edema commonly associated with brain metastases is typically due to increased vascular permeability. This is secondary to blood-brain barrier (BBB) disruption around the lesion(s), and is termed vasogenic edema. BBB disruption is caused by vascular endothelial growth factor overexpression and secretion by metastatic lesions. BBB disruption allows passage of plasma and proteins from the vascular compartment into brain parenchyma, resulting in edema and therefore increased interstitial pressure within and around the tumor. The resulting increase in intracranial pressure (ICP) leads to the classic symptoms of headache, nausea and vomiting [3].

Corticosteroids appear to have a mechanism of action specific to vasogenic edema, as they are relatively ineffective in cytotoxic or intracellular edema. Studies using gadolinium-enhanced magnetic resonance imaging (MRI) in primary and secondary brain tumours suggest that the anti-edema effect of corticosteroids is related to decreasing BBB permeability [4]. After seven days of treatment, a reduction in radiologically-apparent cerebral edema is seen which correlates with a reduction in blood-tumour-barrier transport [4].


Dexamethasone (DXM) is the corticosteroid of choice for treating edema associated with brain metastases because of its biological properties, including half-life and potency [3,5-6]. It has the least mineralocorticoid activity of the agents in this class, which results in a lower rate of peripheral fluid retention [7]. The biological half-life is 36-54 hours, such that frequent dosing is not necessary, and the potency is six times that of methylprednisolone, reducing tablet burden [7,8]. There are also multiple available routes of administration. However, the long half-life may increase the risk of adrenal suppression with long term use. It is also more difficult to taper slowly when sub-physiological dosing is required, due to lack of availability of very low strength formulations [9].

Side Effects

Side effects of DXM are common (Table 1), and they increase in frequency and severity with increased dose and duration of therapy [3].