What is the recommended dosage of Temozolomide (temozolomide) for adults with newly diagnosed glioblastoma multiforme (GBM)?

Temozolomide Dosage for Newly Diagnosed Glioblastoma Multiforme

For adults with newly diagnosed glioblastoma multiforme, temozolomide should be administered at 75 mg/m² daily during the entire 42-day concurrent radiotherapy phase, followed by maintenance dosing at 150-200 mg/m² once daily for 5 consecutive days every 28 days for a maximum of 6 cycles. 1, 2

Standard Dosing Regimen

Concurrent Phase (with Radiotherapy)

• Dose: 75 mg/m² once daily for 42 days 1, 2
• Radiotherapy: 60 Gy in 2 Gy fractions, 5 fractions per week 1
• Duration: Continue throughout the entire radiotherapy course, up to 49 days if toxicity criteria are met 2
• Critical requirement: Pneumocystis pneumonia (PCP) prophylaxis is mandatory during concurrent therapy and must continue until lymphocytopenia recovers to Grade ≤1 1, 2

Continuation criteria during concurrent phase: 2

• Absolute neutrophil count ≥1.5 × 10⁹/L
• Platelet count ≥100 × 10⁹/L
• Non-hematologic toxicity ≤Grade 1 (except alopecia, nausea, vomiting)

Maintenance Phase (Post-Radiotherapy)

Cycle 1: 1, 2

• Begin 4 weeks after completing concurrent chemoradiotherapy
• Dose: 150 mg/m² once daily for 5 days, followed by 23 days without treatment

Cycles 2-6: 1, 2

• Dose escalation: Increase to 200 mg/m² if Cycle 1 toxicity was Grade ≤2 (except alopecia, nausea, vomiting), ANC ≥1.5 × 10⁹/L, and platelets ≥100 × 10⁹/L
• Duration: Maximum of 6 cycles total
• If dose was not escalated at Cycle 2, do not escalate in subsequent cycles 2

Alternative Regimens for Specific Populations

Elderly or Poor Performance Status Patients

Hypofractionated radiotherapy option: 1

• Concurrent dose: 75 mg/m² once daily for 21 days
• Radiotherapy: 40.05 Gy in 15 fractions over 3 weeks
• Maintenance: 150-200 mg/m² once daily for 5 of 28 consecutive days for up to 12 months (note the extended duration compared to standard regimen)

Temozolomide monotherapy (for patients unsuitable for combined modality): 1

• 100 mg/m² once daily on days 1-7 every 2 weeks until progression, OR
• 200 mg/m² once daily on days 1-5 every 28 days for up to 6 cycles

Monitoring Requirements

During concurrent phase: 2

• Complete blood count weekly
• Dose interruption if ANC ≥0.5 and <1.5 × 10⁹/L or platelets ≥10 and <100 × 10⁹/L
• Discontinue if ANC <0.5 × 10⁹/L or platelets <10 × 10⁹/L

During maintenance phase: 2

• Complete blood count on Day 22 (or within 48 hours) of each cycle
• Weekly monitoring until ANC >1.5 × 10⁹/L and platelets >100 × 10⁹/L
• Do not start next cycle until counts recover above these thresholds

Critical Safety Considerations

Common pitfalls to avoid: 1, 2

• Failing to provide PCP prophylaxis during concurrent therapy—this is mandatory, not optional
• Starting maintenance therapy too early (must wait 4 weeks after completing concurrent phase)
• Escalating dose in Cycle 2 without verifying adequate blood counts and acceptable toxicity from Cycle 1
• Continuing treatment without appropriate hematologic monitoring

MGMT promoter methylation status: 1

• Should be assessed as it predicts benefit from temozolomide
• Patients with MGMT promoter methylation derive greater survival benefit
• However, current guidelines support temozolomide use regardless of MGMT status for standard-risk patients under age 70 with good performance status

Evidence Basis

This dosing regimen is derived from the landmark EORTC 26981-22981 trial, which demonstrated improved median survival (14.6 vs 12.1 months) and 2-year survival (26.5% vs 10.4%) compared to radiotherapy alone 1, 3. The FDA approved this regimen based on these results, with a hazard ratio for death of 0.63 (95% CI 0.52-0.75, P<0.001) 4, 3.