Toxicity of concurrent and adjuvant temozolomide in patients with glioblastoma multiforme (GBM).

Abstract

e14037 Background: (MGMT) promotor is prognostic and predictive of temozolomide (TMZ) benefit in newly diagnosed GBM. It has been suggested that MGMT methylation is associated with TMZ toxicity in some cancers such as melanoma but is not clearly defined in GBM. Methods: To investigate this, a retrospective electronic chart review of patients (pts) with resected GBM in a tertiary neurosurgical referral center from 1 July 2017 – 31 Dec 2020 was conducted. Hematological toxicities during TMZ with RT (concurrent) and subsequent TMZ (adjuvant) were assessed and graded by CTCAE V5.0. Toxicity was compared by MGMT methylation status. Results: In a 3.5 year period, 417 GBM resections were performed. Of these, 186 (45%) patients received at least 1 dose of TMZ in our institution: 180 pts received concurrent TMZ, 6 pts received adjuvant only. MGMT was methylated, unmethylated and unknown in 72, 97 and 17 pts respectively. In the concurrent and adjuvant phases respectively, thrombocytopenia incidence was 20%(N=14) and 52%(N=25) in the methylated group and 15%(N=15) and 51%(N=37) in the unmethylated group. In the adjuvant phase, incidence of ≥ grade 3 thrombocytopenia was 8%(N=4), in the methylated patients and 9%(N=7) for those unmethylated. Neutropenia incidence was low in the concurrent phase, however in the adjuvant phase was 29%(N=14) in the methylated group and 23%(N=17) in the unmethylated group. ≥G3 incidence was 10%(N=5) and 3%(N=2) respectively. Conclusions: In this retrospective study, a higher incidence of hematological toxicity was not seen in pts with MGMT methylated tumors. Methylation of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase.[Table: see text]