What is the Stupp protocol for treating newly diagnosed glioblastoma in adults?

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Last updated: September 16, 2026 • View editorial policy

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The Stupp Protocol for Newly Diagnosed Glioblastoma

The Stupp protocol is the standard of care for adults with newly diagnosed glioblastoma who are in good general and neurological condition and aged <70 years, consisting of concomitant radiotherapy (60 Gy in 30 fractions) with daily temozolomide (75 mg/m² for 42 days including weekends) followed by six cycles of adjuvant temozolomide (150-200 mg/m², days 1-5 of each 28-day cycle). 1, 2, 3

Core Treatment Components

Concomitant Phase (6 weeks)

  • Radiotherapy: 60 Gy delivered in 2 Gy fractions, 5 days per week for 6 weeks, targeting the tumor bed or resection site with a 2-3 cm margin 1, 2, 3
  • Concurrent temozolomide: 75 mg/m² daily for 42 days (up to 49 days maximum), starting day 1 of radiotherapy and continuing through weekends 1, 2, 3
  • PCP prophylaxis: Required throughout concomitant phase and continued until lymphocyte recovery to ≤Grade 1 3

Critical safety thresholds during concomitant phase 3:

  • Continue treatment only if: ANC ≥1.5 × 10⁹/L, platelets ≥100 × 10⁹/L, non-hematologic toxicity ≤Grade 1 (except alopecia, nausea, vomiting)
  • Interrupt if: ANC 0.5-1.5 × 10⁹/L or platelets 10-100 × 10⁹/L or Grade 2 non-hematologic toxicity
  • Discontinue if: ANC <0.5 × 10⁹/L or platelets <10 × 10⁹/L or Grade 3-4 non-hematologic toxicity

Maintenance Phase (6 months)

Four weeks after completing chemoradiotherapy 2, 3:

  • Cycle 1: 150 mg/m² once daily for 5 consecutive days, followed by 23 days rest
  • Cycles 2-6: Escalate to 200 mg/m² if Cycle 1 toxicity ≤Grade 2 (except alopecia, nausea, vomiting) and ANC ≥1.5 × 10⁹/L and platelets ≥100 × 10⁹/L 2, 3

Evidence Base

The landmark trial demonstrated this protocol improves overall survival from 12.1 months to 14.6 months (HR 0.63,95% CI 0.52-0.75, P<0.001), with 2-year survival increasing from 10.4% to 26.5% 4. This survival benefit is achieved with minimal additional toxicity—only 7% of patients experienced Grade 3-4 hematologic toxicity during concomitant treatment 4.

Age-Specific Modifications

Patients ≥60-70 Years

For elderly patients with good performance status (KPS ≥70) 1, 2:

  • MGMT unmethylated tumors: Hypofractionated radiotherapy alone (40 Gy in 15 fractions over 3 weeks) 1, 2
  • MGMT methylated tumors: Either hypofractionated radiotherapy (40 Gy in 15 fractions) with concurrent temozolomide (75 mg/m² daily for 21 days) plus adjuvant temozolomide (150-200 mg/m² days 1-5 every 28 days for up to 12 months), OR temozolomide alone (100 mg/m² days 1-7 every 2 weeks or 200 mg/m² days 1-5 every 28 days) 1, 2

The addition of temozolomide to hypofractionated radiotherapy has been shown to improve overall survival in patients aged ≥60 years 1.

MGMT Promoter Methylation Status

The benefit from temozolomide is largely limited to patients with MGMT promoter-methylated glioblastoma 1. However, recent data suggest a minor overall survival prolongation with radiotherapy plus temozolomide versus radiotherapy alone even in elderly patients with unmethylated MGMT promoter, making this consideration somewhat controversial 1.

MGMT promoter methylation testing has become standard practice in many European countries for management decisions, particularly in elderly patients not considered eligible for combined modality treatment 1.

Important Caveats

Dosing Modifications

  • No benefit from increasing temozolomide dose beyond standard dosing 1
  • No benefit from extending chemotherapy beyond six cycles 1
  • Do not reduce dose during concomitant phase; only interrupt or discontinue based on toxicity 3

Tumor-Treating Fields

While a phase III trial showed superior progression-free and overall survival with the addition of tumor-treating fields to maintenance temozolomide 1, 2, this remains highly controversial due to questions about study design (no sham control), mode of action, feasibility, and cost-effectiveness 1. Tumor-treating fields are not widely available in Europe 1.

Bevacizumab

Not recommended for newly diagnosed glioblastoma 1, 5. Two phase III trials showed progression-free survival prolongation (3-4 months) but no overall survival benefit, with concerns about early cognitive decline 1.

Timing Optimization

Recent evidence suggests initiating chemoradiotherapy 32-49 days post-surgery in MGMT-methylated patients may improve outcomes 6. Minimizing dexamethasone exposure (keep <1.2 mg/m² at critical treatment points) also appears beneficial 6.

Patient Selection

Patients with large or multifocal lesions, low KPS, or inability to provide consent after biopsy should receive supportive and palliative care rather than aggressive treatment 1.

References

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.