Glioblastoma

Definition

Glioblastoma (GBM) is a WHO Grade IV astrocytoma, representing the most aggressive primary brain tumor in adults. It arises from astrocytes and is highly infiltrative, making complete surgical resection difficult.

Epidemiology

• Most common primary malignant brain tumor in adults.
• Peak incidence: 45–70 years.
• Slight male predominance.

Pathophysiology / Molecular Markers

• IDH-wildtype: Most GBMs; poor prognosis.
• IDH-mutant GBM: Less common; slightly better prognosis.
• MGMT promoter methylation: Predicts better response to temozolomide.
• EGFR amplification, PTEN loss, TP53 mutations can be present.

Clinical Presentation

• Headache, nausea, vomiting
• Seizures
• Focal neurologic deficits (depending on tumor location)
• Cognitive changes

Standard Treatment

1. Maximal safe surgical resection – to reduce tumor burden.
2. Radiotherapy (RT) – usually 60 Gy in 30 fractions.
3. Concurrent and adjuvant chemotherapy – temozolomide (TMZ):
   • Concurrent: 75 mg/m² daily during RT
   • Adjuvant: 150–200 mg/m²/day for 5 days every 28 days, typically 6–12 cycles

Recurrent GBM options:

• Bevacizumab (anti-VEGF)
• Lomustine (CCNU)
• Clinical trials (CAR-T, tumor-treating fields, experimental targeted therapy)

Pharmacist-Relevant Considerations

• Temozolomide: myelosuppression (monitor CBC), nausea (antiemetics recommended), minimal CYP interactions.
• Corticosteroids (dexamethasone): used to control cerebral edema; monitor glucose, infection risk, GI protection.
• Seizure prophylaxis: Levetiracetam preferred due to low interaction potential.
• Supportive care: Antiemetics, PJP prophylaxis if prolonged immunosuppression, monitoring for infection.
• Drug interactions: Watch additive myelosuppression with concurrent therapies.