Is Temozolomide (chemotherapy) given as adjuvant chemotherapy (CT) or upfront first-line treatment in brain tumors?

Temozolomide in Brain Tumors: Timing of Administration

Temozolomide is given as BOTH concurrent (upfront first-line) and adjuvant chemotherapy in glioblastoma—it is administered daily during radiotherapy (concurrent phase) and then continued as maintenance therapy for 6-12 cycles after radiation completion (adjuvant phase). 1, 2

Standard Treatment Protocol for Glioblastoma

The established regimen consists of two distinct phases:

Concurrent Phase (Upfront First-Line)

• Temozolomide 75 mg/m² daily for 42 days administered simultaneously with focal radiotherapy (60 Gy in 30 fractions) 1, 2
• This represents the upfront first-line chemotherapy component, given immediately after surgical resection 1
• No dose reductions are recommended during this phase, though interruptions may occur based on toxicity 2
• PCP prophylaxis is required during concurrent administration 2

Adjuvant/Maintenance Phase

• Begins 4 weeks after completing radiotherapy 2
• Cycle 1: 150 mg/m² daily for 5 days, followed by 23 days rest 2
• Cycles 2-6: Escalate to 200 mg/m² if tolerated (based on toxicity and blood counts) 2
• This is the adjuvant chemotherapy component 1

Patient-Specific Considerations

Age ≤70 Years with Good Performance Status (KPS ≥70)

• Concurrent and adjuvant temozolomide with radiotherapy is Category 1 recommendation 1
• This represents the highest level of evidence-based standard of care 1

Age >70 Years with Good Performance Status

• Concurrent and adjuvant temozolomide with hypofractionated RT (40 Gy/15 fractions) is recommended 1
• This combination significantly improves overall survival (9.3 vs 7.6 months) and progression-free survival (5.3 vs 3.9 months) compared to RT alone 1
• Category 2A recommendation for this age group 1

Poor Performance Status (KPS <70)

• Temozolomide alone (without concurrent RT) is an option, particularly if MGMT promoter is methylated 1
• This represents chemotherapy with deferred radiation 1

Duration of Adjuvant Therapy

While FDA approval and initial trials focused on 6 cycles of adjuvant temozolomide, extending treatment to 12 cycles is increasingly common in clinical practice 1, 2

• Population-based data suggests extended adjuvant therapy (>6 cycles) improves median survival from 16.5 to 24.6 months without increased toxicity 3
• Treatment should continue as long as patients maintain stable disease with acceptable toxicity 3, 4

Critical Distinction from Other Gliomas

Anaplastic Astrocytoma (Grade III)

• Temozolomide can be used as monotherapy (deferred radiation) or with concurrent RT 1
• This differs from glioblastoma where concurrent chemoradiation is standard 1

Anaplastic Oligodendroglioma with 1p/19q Codeletion

• PCV (procarbazine, lomustine, vincristine) is preferred over temozolomide 1, 5
• Temozolomide is designated Category 2B for this indication 1

Common Pitfalls to Avoid

• Do not confuse "adjuvant" with "after all treatment is complete"—in glioblastoma, temozolomide is both concurrent (during RT) and adjuvant (after RT) 1, 2
• Pseudoprogression can occur within 3 months after completing RT, mimicking tumor progression when treatment is actually effective 1, 6
• MGMT promoter methylation status should guide treatment decisions, particularly in elderly patients and those with poor performance status 1
• Stopping temozolomide at 6 cycles when patients are tolerating treatment well and maintaining stable disease may represent undertreatment 3