Is the Patient with Glioblastoma Receiving Chemotherapy (Temozolomide)?
Yes, patients with glioblastoma should receive temozolomide as the standard chemotherapy, administered concurrently with radiotherapy (75 mg/m² daily for up to 42-49 days) followed by adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days for 6 cycles). 1, 2
Standard Treatment Protocol for Newly Diagnosed Glioblastoma
The Stupp protocol represents the current standard of care for glioblastoma patients aged ≤70 years with good performance status. 3, 1 This consists of:
Concurrent phase: Temozolomide 75 mg/m² daily starting on the first day of radiotherapy and continuing until the last day (maximum 42-49 days), administered simultaneously with focal radiotherapy (60 Gy in 30 fractions) 1, 2
Adjuvant phase: Beginning 4 weeks after completion of radiotherapy, temozolomide 150-200 mg/m² on days 1-5 of each 28-day cycle for 6 cycles 1, 2
Dose escalation: If absolute neutrophil count ≥1.5 × 10⁹/L and platelet count ≥100 × 10⁹/L on day 29, increase from 150 mg/m² to 200 mg/m² 2
This regimen demonstrated a statistically significant survival benefit with a hazard ratio of 0.63 (95% CI: 0.52-0.75, P<0.0001), increasing median survival by 2.5 months compared to radiotherapy alone. 2
Age-Specific Considerations
For patients >70 years with good performance status, concurrent and adjuvant temozolomide with hypofractionated radiotherapy (e.g., 40 Gy in 15 fractions) significantly improves overall survival and progression-free survival compared to radiotherapy alone. 3, 1
For elderly patients with poor performance status, temozolomide monotherapy is an option, particularly if MGMT promoter methylation is present. 3, 1 However, radiotherapy alone may be preferred for patients with unmethylated MGMT promoter. 3
Critical Distinction: Glioblastoma vs. Other High-Grade Gliomas
Temozolomide use differs significantly based on tumor type:
Glioblastoma (WHO grade IV): Concurrent chemoradiation with temozolomide is the standard of care 3, 1
Anaplastic astrocytoma (WHO grade III): Radiotherapy is standard; temozolomide can be used as monotherapy or with concurrent radiotherapy, but evidence is weaker 3, 1
Anaplastic oligodendroglioma with 1p/19q codeletion: PCV chemotherapy is preferred over temozolomide (temozolomide is Category 2B for this indication) 3, 1
Alternative Chemotherapy Options
For patients who cannot receive temozolomide, alternative options include:
Nitrosourea-based chemotherapy (lomustine, carmustine) as monotherapy, though this showed only marginal survival benefit in meta-analyses 3
Carmustine wafers (Gliadel) implanted in the resection cavity, which provide modest survival benefit but lack comparison data with standard temozolomide/radiotherapy 3
PCV regimen (procarbazine, lomustine, vincristine) failed to improve survival in glioblastoma in randomized trials 3
Common Pitfalls and Caveats
Myelosuppression monitoring is essential: Thrombocytopenia is the main dose-limiting toxicity, requiring regular blood count monitoring during treatment. 3 Hepatic function must also be monitored regularly. 3
Pneumocystis pneumonia prophylaxis is required during concurrent temozolomide/radiotherapy regardless of lymphocyte count, continuing until lymphocyte recovery to ≤Grade 1. 2
Treatment resistance is common: 60-75% of glioblastoma patients derive no benefit from temozolomide, primarily due to MGMT overexpression or DNA repair pathway deficiencies. 4, 5 MGMT promoter methylation status can help predict benefit, though prospective validation is ongoing. 3
Extended adjuvant therapy beyond 6 cycles (up to 12 cycles) is increasingly common in clinical practice, though FDA approval and initial trials focused on 6 cycles. 1
Pseudoprogression can occur 4-8 weeks after radiotherapy completion and should be re-evaluated with repeat MRI 4 weeks later before discontinuing chemotherapy. 3