Effects of temozolomide dosing on outcome in glioblastoma

Temozolomide (TMZ) with concomitant radiation is the standard therapy for treating glioblastomas (GBM) and is dosed based on body surface area (BSA) using a goal dose of 75 mg/m². Neurooncologists have different methods of dosing patients, with some dosing within 5 mg of the calculated dose and others rounding to reduce patient burden. We aimed to determine the effect of rounded doses of TMZ on survival.

We conducted a single-center retrospective review of 380 patients with GBM from 2013 to 2024. Relevant data was extracted from electronic medical records. Kaplan-Meier curves and Cox regression models were used to determine survival outcomes.

No significant impact on survival outcomes was observed when distance from the calculated temozolomide dose was analyzed as a continuous variable (p = 0.156), adjusting for MGMT, the extent of resection, radiation fractions, and Karnofsky performance scores (KPS). Even limited to just MGMT-methylated tumors, TMZ dose did not affect survival. BMI had no impact on survival outcomes. Our subgroup analysis revealed that patients with MGMT-methylated tumors, total resection, higher KPS, and ≥ 30 radiation fractions had improved survival (p < 0.01). Dose interruptions were not more likely with doses above 75 mg/m² (14%) than with doses at or below 75 mg/m² (9%) (p = 0.22).

Rounding temozolomide doses does not significantly impact survival outcomes or risk of treatment interruptions for patients with GBM. These findings may allow neuro-oncologists to prioritize reducing pill burden and treatment costs without compromising patient outcomes.