[Chemotherapy for malignant gliomas: an update]

Area of Science:

• Neuro-oncology
• Cancer biology
• Pharmacology

Context:

• Gliomas represent the most common primary brain tumors, accounting for 30% of CNS tumors.
• High-grade gliomas, particularly glioblastoma (GBM), have a dismal prognosis despite aggressive multimodal therapy.
• Current treatments, including older alkylating agents like ACNU and MCNU, offer limited clinical benefit for malignant gliomas.

Purpose:

• To review the current landscape of malignant glioma treatment, focusing on the role of temozolomide (TMZ) and emerging combination therapies.
• To highlight the importance of O6-methylguanine-DNA methyltransferase (MGMT) status in predicting TMZ efficacy.
• To discuss the potential of combination therapies, such as TMZ with anti-VEGF agents, in improving outcomes for glioma patients.

Summary:

• Temozolomide (TMZ), an oral alkylating agent, has become a first-line therapy for malignant gliomas in Japan since 2006, demonstrating improved survival rates.
• Clinical outcomes with TMZ are significantly influenced by the patient's O6-methylguanine-DNA methyltransferase (MGMT) status, suggesting MGMT modification as a future therapeutic target.
• Combination therapies involving TMZ with other agents, notably anti-vascular endothelial growth factor (VEGF) antibodies, are under investigation and show potential to enhance treatment efficacy beyond TMZ plus radiotherapy.

Impact:

• Future research should focus on phase II to III clinical trials to validate the efficacy of novel combination therapies for malignant brain tumors.
• Understanding MGMT status is crucial for personalizing TMZ treatment and maximizing clinical benefits.
• Advancements in combination therapies hold the potential to significantly improve the survival and quality of life for patients with malignant gliomas.