What is the best chemotherapy for glioblastoma?

From the Guidelines

Temozolomide is the standard chemotherapy for glioblastoma, typically administered at 75 mg/m² daily during radiation therapy, followed by maintenance therapy at 150-200 mg/m² for 5 days every 28-day cycle for 6-12 cycles, as it has been shown to improve overall survival and progression-free survival compared to radiation therapy alone 1.

Key Points

• The Stupp protocol, which combines temozolomide with radiation therapy, is the standard of care for newly diagnosed glioblastoma in patients up to 70 years of age 1.
• Temozolomide works by alkylating DNA, damaging the genetic material of rapidly dividing cancer cells and triggering cell death, with its effectiveness enhanced in patients with methylation of the MGMT gene promoter 1.
• Common side effects of temozolomide include nausea, fatigue, and bone marrow suppression, making regular blood count monitoring essential 1.
• For recurrent glioblastoma, options include bevacizumab, lomustine, or enrollment in clinical trials testing novel agents, although bevacizumab has not been shown to improve overall survival and may be associated with a higher incidence of early adverse events 1.

Treatment Considerations

• The addition of concurrent and adjuvant temozolomide to fractionated radiotherapy has been shown to improve overall survival and progression-free survival compared to fractionated radiotherapy alone, with a reasonably low incidence of early adverse events and without impairing quality of life 1.
• The impact of bevacizumab on health-related quality of life requires further validation, and its routine addition to standard therapy for newly diagnosed glioblastoma is not recommended outside a clinical trial 1.
• The most recent and highest quality study, published in 2021, confirms the use of temozolomide as the standard chemotherapy for glioblastoma, with a favorable safety profile and the main dose-limiting toxicity being myelosuppression 1.

From the FDA Drug Label

The addition of concomitant and maintenance temozolomide to radiotherapy in the treatment of patients with newly diagnosed GBM showed a statistically significant improvement in overall survival compared to radiotherapy alone ( Figure 1). The hazard ratio (HR) for overall survival was 0.63 (95% CI for HR=0.52 to 0.75) with a log-rank P<0. 0001 in favor of the temozolomide arm. The median survival was increased by 2.5 months in the temozolomide arm.

Avzivi is indicated for the treatment of: ... Recurrent glioblastoma in adults. ( 1.3)

Temozolomide and bevacizumab are both used in the treatment of glioblastoma.

• Temozolomide is used in combination with radiotherapy for the treatment of newly diagnosed glioblastoma, and has shown a statistically significant improvement in overall survival compared to radiotherapy alone 2.
• Bevacizumab is indicated for the treatment of recurrent glioblastoma in adults 3.

It is not possible to determine the "best" chemotherapy for glioblastoma based on the provided information, as this would depend on various factors such as the patient's overall health, the specific characteristics of the tumor, and the treatment goals.

From the Research

Chemotherapy Options for Glioblastoma

The treatment of glioblastoma often involves a combination of surgery, radiation, and chemotherapy. When it comes to chemotherapy, several options are available, each with its own efficacy and safety profile.

• Temozolomide: This is a commonly used chemotherapeutic agent for glioblastoma, particularly in the first-line setting 4. It is often administered concurrently with radiation therapy, followed by adjuvant temozolomide for a specified number of cycles, as per the Stupp protocol.
• Lomustine: This nitrosourea-based chemotherapy has shown promise in the treatment of recurrent glioblastoma, especially in patients with tumors having O6-methylguanine DNA methyltransferase (MGMT) promoter methylation 5.
• Lomustine-Temozolomide Combination: Research suggests that combining lomustine with temozolomide may improve survival in patients with newly diagnosed glioblastoma and methylated MGMT promoter compared to standard temozolomide therapy alone 6.

Efficacy and Safety Considerations

The choice of chemotherapy for glioblastoma depends on various factors, including the patient's overall health, the specific characteristics of the tumor, and the stage of the disease.

• Efficacy: Studies have demonstrated the efficacy of temozolomide in improving survival in patients with glioblastoma, including those with newly diagnosed and recurrent disease 7, 4.
• Safety: Chemotherapy for glioblastoma can be associated with significant side effects, including hematological toxicity, digestive tract reactions, and fatigue 5, 8. The safety profile of low-dose temozolomide maintenance therapy in elderly patients has been explored, suggesting it may be a viable option with tolerable adverse reactions 8.

Ongoing Research and Future Directions

Continued research is necessary to optimize chemotherapy regimens for glioblastoma, including exploring combination therapies and identifying biomarkers to predict treatment response.

• Combination Therapies: Investigating the efficacy of combining different chemotherapeutic agents, such as lomustine and temozolomide, is an area of active research 6.
• Biomarkers: Identifying practical biomarkers for predicting susceptibility to specific chemotherapies, like temozolomide, is crucial for personalized treatment approaches 7.