What is the role of dexamethasone in managing symptoms for a patient with glioblastoma multiforme?

Dexamethasone for Glioblastoma Multiforme

Dexamethasone should be used selectively and at the lowest effective dose (4-8 mg/day) only in symptomatic glioblastoma patients with cerebral edema, and tapered rapidly once symptoms improve, as higher doses and prolonged use are associated with significantly worse survival outcomes. 1, 2

When to Initiate Dexamethasone

Use dexamethasone only in symptomatic patients with neurological deficits from mass effect or cerebral edema—not prophylactically in asymptomatic patients, even if imaging shows edema. 1, 3

Dosing Based on Symptom Severity:

• Mild symptoms (headache, minimal focal deficits): Start dexamethasone 4-8 mg/day as a single daily dose 1
• Moderate to severe symptoms (significant mass effect, signs of increased intracranial pressure): Start dexamethasone 16 mg/day or higher 1
• Asymptomatic patients: Do not use steroids—no benefit and significant toxicity 1, 3

Critical Evidence on Survival Impact

Higher dexamethasone doses and prolonged use are strongly associated with worse outcomes. A 2024 meta-analysis of 22 retrospective studies demonstrated that higher dexamethasone doses correlated with significantly poorer overall survival (hazard ratio 1.62,95% CI 1.40-1.88) and progression-free survival (hazard ratio 1.49,95% CI 1.23-1.81). 2 This survival detriment persisted even after correcting for clinical status (HR 1.52,95% CI 1.38-1.67). 2

A 2015 retrospective analysis of 73 newly diagnosed glioblastoma patients showed that dexamethasone use during concurrent radiation and temozolomide reduced overall survival (12.7 vs 22.6 months, p=0.003) and progression-free survival (3.6 vs 8.4 months, p<0.0001). 4 On multivariable analysis, dexamethasone predicted an unfavorable overall survival hazard ratio of 1.72 (p=0.045). 4

Tapering Strategy

Taper dexamethasone as rapidly as clinically tolerated—typically over 2-4 weeks—to minimize toxicity. 1, 3 The ESMO guidelines explicitly state: "Rapid tapering and discontinuation of corticosteroids is recommended in order to avoid toxicity associated with prolonged exposure to steroids, e.g. myopathy and weakness, lymphopenia and risk of infection, osteoporosis and Cushing syndrome." 1

• After tumor resection, there is no need for prolonged steroid therapy in asymptomatic patients 1
• No prophylaxis needed during radiotherapy in asymptomatic patients 1
• Never abruptly discontinue after prolonged use (>2 weeks) due to risk of adrenal insufficiency and rebound edema 3

Why Dexamethasone is Preferred

Dexamethasone is the corticosteroid of choice due to its potent glucocorticoid activity with minimal mineralocorticoid effects, avoiding fluid retention and electrolyte disturbances. 1, 3

Mandatory Safety Measures

Gastrointestinal Prophylaxis:

Initiate proton pump inhibitor or H2-receptor blocker immediately to prevent gastrointestinal bleeding, especially if patient is on anticoagulation. 5

Infection Prophylaxis:

Start trimethoprim-sulfamethoxazole prophylaxis if steroid therapy will exceed 4 weeks, or if patient receives concurrent radiation/chemotherapy, or has lymphocyte count <1000/mL. 3

Monitoring Requirements:

Monitor closely for hyperglycemia, hypertension, psychiatric symptoms, myopathy, opportunistic infections, and osteoporosis. 1, 3

Critical Pitfalls to Avoid

• Do not use prophylactic steroids in asymptomatic patients—no benefit, only toxicity 1, 6, 3
• Avoid doses above 8 mg/day in mild-moderate symptoms—minimal additional benefit with linearly increasing toxicity 5
• Do not delay tapering—prolonged exposure (>3 weeks) causes significant immunosuppression, metabolic derangements, and potentially inferior survival 3, 2
• Avoid night-time dosing to minimize sleep disturbance and HPA axis suppression 6
• Do not use steroids if ischemic stroke is suspected—ineffective and potentially harmful in that context 5

Special Consideration: Bevacizumab

The detrimental survival effect of dexamethasone may be mitigated by concurrent bevacizumab administration. In patients receiving temozolomide and bevacizumab with radiation, dexamethasone did not reduce overall survival (22.9 vs 22.8 months, p=0.48). 4 However, bevacizumab is not standard for newly diagnosed glioblastoma and should not be used solely to permit higher steroid doses.

Postoperative Management

After surgical resection, reassess the need for steroids immediately—maximum dose of 16 mg daily (divided into 4 equal doses) for symptomatic patients, started by the neurosurgeon, with rapid tapering where appropriate. 7 Patients with high-grade tumors who remain symptomatic can be maintained on 0.5-1.0 mg daily. 7