Survival benefit of levetiracetam in glioblastoma treatment: a prospective, single center, and single arm study

Chae-Yong Kim 1 ,2, Tackeun Kim1, Jung Ho Han1, Yu Jung Kim1, In Ah Kim1 ,2, Chang-Ho Yun1, Hee Won Jung2
1Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea, 2Seoul National University College of Medicine, Seoul, Republic of Korea

Although the inhibition O-6-methylguanine-DNA methyltransferase (MGMT) by levetiracetam (LEV) was established in vitro, the survival benefit of LEV has not been studied clinically. This study was performed to assess survival benefit of LEV as a chemo-sensitizer of temozolomide for glioblastoma patients compared with that of other anti-convulsant such as valproic acid (VPA). A total of 38 consecutive patients who underwent concomitant chemoradiotherapy for primary supratentorial glioblastoma and were administered LEV before adjuvant chemotherapy with temozolomide was prospectively collected. Forty-two consecutive patients taking VPA with same disease and chemoradiotherapy protocol were enrolled as a control group. The distributions of gender, age, extended lesion, Karnofsky performance scale (KPS) score, extent of removal and methylation status of MGMT promoter were not different between LEV and control group. The median progression-free and overall survival (PFS and OS) of the LEV group (9.3 months (95% CI, 7.3 – 11.3) and 25.7 months (95% CI, 21.1 – 30.3), respectively) were significant longer than those of the control group (6.5 months (95% CI, 5.6 – 7.4) and 16.4 (11.8 – 21.0), respectively) (p = 0.019 and 0.027, respectively). Significant prognostic factors for OS of the all the 80 patients were preoperative KPS score (p=0.027; HR=0.360), the methylation status of MGMT promoter (p=0.002; HR=0.203), and LEV (p=0.004; HR=0.244) in the multivariate analysis. LEV may present survival benefit in glioblastoma patients who receive temozolomide-based chemotherapy compared with other anti-epileptic drug such as VPA. Prospective randomized study is needed.