Survival benefit of levetiracetam in patients treated with concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma multiforme

Abstract

BACKGROUND: A chemosensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O-6 methylguanine-DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. The objective of this study was to assess the survival benefit of LEV compared with other antiepileptic drugs as a chemosensitizer to temozolomide for patients with glioblastoma. METHODS: In total, 103 consecutive patients with primary glioblastoma who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and 58 patients (56%) received LEV during temozolomide chemotherapy for at least 3 months. A Cox regression survival analysis was performed to adjust for confounding factors, including age, extent of lesion, Karnofsky performance scale score, extent of removal, and MGMT promoter methylation status. RESULTS: The median progression-free survival (PFS) and overall survival (OS) for patients who received LEV in combination with temozolomide (PFS: median, 9.4 months; 95% confidence interval [CI], 7.5-11.3 months; OS: median, 25.7 months; 95% CI, 21.7-29.7 months) were significantly longer than those for patients who did not receive LEV (PFS: median, 6.7 months; 95% CI, 5.8-7.6 months; OS: median, 16.7 months; 95% CI, 12.1-21.3 months; P 5.010 and P 5.027, respectively). In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (hazard ratio [HR], 0.37; P 5.016), MGMT promoter methylation (HR, 0.30; P 5.002), and receipt of LEV (HR, 0.31; P <.001. CONCLUSIONS: LEV may provide a survival benefit in patients with glioblastoma who receive temozolomide-based chemotherapy. A prospective randomized study may be indicated. Cancer 2015;121:2926-32.

In vitro antineoplastic effects of brivaracetam and lacosamide on human glioma cells

“…For this reason a possible intrinsic antineoplastic effect of these drugs would be useful. In addition to the anticonvulsant mechanism, some AED have been previously described to exert a cytotoxic effect that, added to the effects of conventional chemo-radiotherapy, possibly impacts also on the survival of these patients [10, 16, 17]. Our results show that BRV and LCM in vitro exert a dose-dependent cytotoxic effect on various glioma cell lines and this effect was concomitant with the modulation of a number of miRNAs.…”

“…Bobustuc and colleagues reported that levetiracetam inhibited in vitro human glioma cell proliferation through p53-mediated MGMT inhibition, thus increasing glioma cell sensitivity to temozolomide [10]. Moreover, in a recent clinical study, Kim and colleagues showed that patients with glioblastoma receiving temozolomide-based chemotherapy and levetiracetam for seizure control, experienced a significant survival benefits [16]. Our in vitro data suggest that some characteristics of the parent drug levetiracetam might be shared by BRV, however further study is needed to verify the effect of BRV on MGMT expression.…”

“…Recently, Kim analysed the benefit of LEV compared with other AED as a chemosensitizer to TMZ for patients with GBM [16]. The median PFS and OS for patients who received LEV in combination with TMZ were significantly longer than those for patients who did not receive LEV (6.7 vs 9.4 months and 16.7 vs 25.7 months respectively).…”

Regression of a glioblastoma multiforme: spontaneous versus a potential antineoplastic effect of dexamethasone and levetiracetam

“…In a single institutional retrospective study, Kim et al 23 noticed that the median progression-free survival (PFS) and OS for patients who received LEV in combination with TMZ was significantly prolonged compared to those who did not receive LEV (PFS 9.4 vs 6.7 months, p=0.010; OS 25.7 vs 16.7 months, p=0.027).…”

Does the choice of antiepileptic drug affect survival in glioblastoma patients?

“…There are several studies on the impact of different AEDs on GBM survival [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Previous research reports that valproate use improves survival in GBM patients [11,12,[17][18][19].…”