Evaluation of the use of metronomic temozolomide for the treatment of recurrent high-grade gliomas

Introduction: High-grade gliomas represent a significant portion of Central Nervous System tumors, with Glioblastoma Multiforme (GBM) being the most common subtype. The median survival for patients treated with standard therapy is 12 months. Within this time period, tumor recurrence is common, and the optimal rescue-therapy remains under investigation. The use of metronomic Temozolomide (mTMZ) at tumor recurrence has been described in studies as a safe and well-tolerated treatment option.

Objective: The aim of this study was to assess the efficacy and toxicities of mTMZ in the treatment of high-grade gliomas at a tertiary public university hospital in Brazil.

Method: All patients treated at our center between January 2014 and June 2024 were retrospectively reviewed. The main inclusion criteria were initial standard therapy at diagnose with surgery followed by chemoradiotherapy; relapse after the first or subsequent line of therapy and treatment with mTMZ 50 mg/m² continuously.

Results: A total of 51 patients were enrolled, 37 men (72%) and 14 women (28%). The median age at diagnosis was 42 years. The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was <2 in 32 patients (62%). Total tumor resection surgery was performed in 25 patients (49%), and the number of adjuvant TMZ cycles was <6 in 21 patients (41%). The number of treatment lines was <2 in 48 patients (94%). The number of metronomic TMZ cycles was >6 in 23 patients (45%). Four patients achieved partial response (7%), 11 had stable disease (21%) and 28 experienced disease progression at first revaluation (54%). The median Overall Survival (OS) for GBM patients was 15.5 months. The median Progression-Free Survival (PFS) was 2 months. In univariate analysis, the use of mTMZ after at least 2 months of the end of adjuvant treatment (“Rechalleng”) was associated with OS (Hazard Ratio 0.24, Confidence Interval 0.11 to 0.55, p = 0.001). Other factors did not reach statistical significance for PFS or OS. Forty-four patients (86%) experienced light-mild toxicities (grade 1-2). The most common Grade 3 toxicities were hematological (3.8%) and nausea (11.5%). Grade 4 toxicities were not observed in any patient. Treatment was discontinued due to refractory toxicities in 2 patients (3%).

Conclusion: mTMZ rechallenge is a viable and well-tolerated treatment modality for recurrent gliomas. It has successfully been able to achieve radiological response and disease control in these patients.

Corresponding author: Felipe Alencar Monteiro Borges (e-mail: amborges.felipe@gmail.com).