Low-dose fotemustine for recurrent malignant glioma: a multicenter phase II study

Area of Science:

• Neuro-oncology
• Clinical Pharmacology
• Cancer Therapeutics

Background:

• Recurrent malignant gliomas (RMGs) are challenging to treat.
• Conventional fotemustine doses (100 mg/m²) show efficacy but cause significant myelotoxicity.
• This toxicity is often not justified in the palliative setting for RMGs.

Purpose of the Study:

• To evaluate a reduced-dose fotemustine regimen (60 mg/m² induction, 75 mg/m² maintenance) for RMGs.
• To assess if this lower dose preserves clinical activity while improving tolerance.
• To explore the role of O(6)-methylguanine methyltransferase (MGMT) gene promoter methylation.

Main Methods:

• A study involving 40 patients with RMGs pretreated with ≤2 chemotherapy lines.
• Administration of fotemustine at induction (60 mg/m²) and maintenance (75 mg/m²) doses.
• Analysis of MGMT gene promoter methylation status in available tumor tissue.

Main Results:

• A disease-control rate of 52.5% (20% partial response, 32.5% stabilization).
• 21% of patients were progression-free at 6 months.
• Severe (Grades 3-4) hematologic toxicity occurred in ≤10% of patients, with no treatment discontinuations due to toxicity.

Conclusions:

• Reduced-dose fotemustine demonstrates comparable activity to full-dose regimens for RMGs.
• The low-dose regimen offers superior tolerability and should be preferred in the palliative setting.
• The impact of MGMT methylation on fotemustine sensitivity requires further investigation.