To evaluate the safety and tolerability of re-exposure to Temozolomide (TMZ) using a daily regimen of 50 mg/m² in patients with gliomas who developed toxicities with standard dosing.

TMZ is the most commonly used chemotherapy in neuro-oncology, typically administered at 75 mg/m² daily during the concurrent phase and at 150–200 mg/m² for 5 days every 28 days during the adjuvant phase (standard TMZ). Up to 15–20% of patients develop dose-limiting toxicities, which may lead to treatment interruption. As continuous TMZ at 50 mg/m² (daily TMZ) has shown fewer toxicities, our center adopted this regimen for patients who developed toxicity on standard TMZ. This study evaluates the safety and tolerability of TMZ re-exposure using this alternative schedule.

We retrospectively reviewed patients treated at the Odette Cancer Centre from 2015–2025 who received daily TMZ after hematologic or clinical toxicities during concurrent or adjuvant standard TMZ. Demographic, clinical, and laboratory data were collected. Hematologic parameters before and after the switch were compared. Toxicities were graded per CTCAE v5.0, and survival analyzed using the Kaplan–Meier method.

25 were included (median age = 62 years); 20 had glioblastoma. The main reasons for switching were hematologic toxicities (48%) and fatigue (40%). After transitioning, only 2 patients (8%) discontinued due to recurrent toxicity, while 44% completed a median of 4 additional cycles; the remainder stopped TMZ due to disease progression. Among patients with hematologic toxicity, platelet and neutrophil nadirs improved significantly after switching (p < 0.001 and p = 0.036, respectively). No hepatic toxicity or opportunistic infections were observed. In glioblastoma patients, median overall survival was 17.0 months (95% CI, 14.6–19.4).

Switching to daily TMZ is a feasible and well-tolerated strategy for patients with gliomas who develop toxicity on standard dosing. This regimen allows continuation of therapy without the need for supportive agents and without compromising survival.