Table 1 Overview of studies on lacosamide, lamotrigine, levetiracetam, topiramate and valproic acid in brain tumor related epilepsy (studies that included ≥ 25 patients on adults with ≥ 3 months observation time)
Article | No. of patientsa | Study design | Type of tumor | Mono-/polytherapy | Follow-up (months) | Outcome/main endpoints |
|---|---|---|---|---|---|---|
Lacosamid | ||||||
Maschio et al. (2017) [57] | 25 | Pros | Glioma “High-grade” n = 12 “Low-grade” n = 13 | Poly | 5.8 (mean) | Seizure free at final follow-up: 28% Reduction of seizures ≥ 50%: 48% (additional to seizure free patients) |
Mo et al. (2022) [63] | 132 | Retro | Primary brain tumor | Mono | Follow up at 3 and 6 months | 3-months seizure-free: 64.4% 6-months seizure-free: 55% |
Van Opijnen et al. (2021)b [48] | 78 | Retro | Glioma Grade 2 (n = 31) Grade 3 (n = 11) Grade 4 (n = 36) | Poly (71%) | Maximum of 36 months | 12-months cumulative incidence of treatment failure: 30% 12-months cumulative incidences of treatment failure uncontrolled seizures: 11% 12-months cumulative incidences of treatment failure due to adverse events: 19% |
Ruda et al. (2017) [58] | 71 | Pros | Glioma Grade 2 (n = 26) Grade 3 (n = 20) Grade 4 (n = 25) | Poly | Follow-up at 3, 6, 9 months | 3-, 6- and 9-months seizure reduction ≥ 50%: 74.6, 76.0, 86.2% (including seizure free patients) 3-, 6- and 9-months seizure free: 42.2, 43.0, 50% |
Ruda et al. (2020) [59] | 93 | Pros | Glioma “Low-grade” (n = 84) Grade 3 (n = 1) Suspected glioma (n = 3) Meningeoma (n = 3) Other (n = 2) | Poly | 6 months observation | 6-months seizure reduction ≥ 50%: 76.7% 6-months improvement of Patient’s Global Impression of Change (PGIC): 64.5% 6-months seizure-free: 34.9% |
Saria et al. (2013) [60] | 70 | Retro | Glioma Grade 2 (n = 25) Grade 3 (n = 12) Grade 4 (n = 28) Meningeoma (n = 3) Other (n = 2) | Poly | 6.2 (median) | Decrease in seizures: 66% 6-months seizure reduction ≥ 50%: 54% No reported toxicities: 77% |
Sepulveda-Sanchez et al. (2016) [61] | 39 | Retro | Primary brain tumor (n = 31) Metastasis (n = 7) Not reported (n = 1) | Poly | Follow-up at 3 and 6 months | 6-months reduction of seizure frequency from 26.4 (mean) to 9.4 (mean) Adverse event: 12% |
Villanueva et al. (2016) [62] | 105 | Retro | “Astrocytoma” (n = 42) Glioblastoma (n = 13) Brain metastasis (n = 11) Meningioma (n = 11) Oligodendroglioma (n = 7) Ganglioglioma (n = 6) Oligoastrocytoma (n = 5) DNET (n = 3) Other (n = 4) | Poly | 6 months observation | 6 months seizure-free: 30.8% 6-months seizure reduction ≥ 50%: 66.3% (including seizure free patients) Adverse events: 41.9% |
Lamotrigin | ||||||
Van Opijnen et al. 2021b [48] | 61 | Retro | Glioma Grade 2 (n = 31) Grade 3 (n = 13) Grade 4 (n = 17) | Poly (66%) | Maximum of 36 months | 12 months cumulative incidence of treatment failure: 38% 12 months cumulative incidences of treatment failure due to uncontrolled seizures: 18% 12 months cumulative incidences of treatment failure due to adverse events: 17% |
Levetiracetam | ||||||
De Groot et al. (2011) [49] | 40 (n = 34 evaluable) | Pros | Glioma Grade 2 (n = 7) Grade 3 (n = 12) Grade 4 (n = 15) | Mono | 6 months observation | 6-months seizure free: 59% 6-months seizure reduction ≥ 50%: 74% |
Kerkhof et al. (2013)d [7] | 36 | Retro | Glioblastoma (n = 36) | Mono | 9 (median) | Seizure free at the end of follow-up (minimum of 6 months): 69.5% |
Maschio et al. (2011) [50] | 29 | Pros | Glioma Grade 2 (n = 6) Grade 3 (n = 10) Grade 4 (n = 9) Meningeoma (n = 2) Other (n = 2) | Mono | 12-months seizure freedom for n = 15 patients who reached this endpoint: 93.3% 12-months ≥ 50% seizure reduction: 6.7% (responder rate 100%) | |
Rosati et al. (2010) [52] | 82 | Pros | Glioma: Grade 1/2 (n = 13) Grade 3 (n = 15) Grade 4 (n = 54) | Mono | 13.1 (mean) | Seizure free with monotherapy levetiracetam at last follow up: 89% |
Rossetti et al. (2013) [53] | 25 | Pros | Glioma Grade 3 or 4 (n = 17) No further details | Mono (n = 9) Poly (n = 14) | 12 months observation | Composite endpoint (discontinuation of the study drug, add-on of a further ASM, ≥ 2 seizures with impaired consciousness) during 1 year follow-up: 36% Discontinuation due to side effects: 24% |
Van der Meer et al. (2020)c [55] | 429 | Retro | Glioma, grade 2–4 Grade 2 (n = 108) Grade 3 (n = 44) Grade 4 (n = 277) | Mono | 86.2 (median) | Treatment failure for any reason within 36-months follow-up: 40% Treatment failure because of AE within 36-months follow-up: 16% Treatment failure because of uncontrolled seizures within 36-months follow-up: 19% |
Wagner et al. (2003) [54] | 26 | Pros | Glioma Grade 3 and 4 (n = 18) Grade 2 (n = 8) | Poly (n = 25) Mono (n = 1) | 9.3 (median) | Seizure free 38% 6-months ≥ 50% seizure reduction: 35% |
Topiramat | ||||||
Maschio et al. (2007) [84] | 47 (45 evaluable) | Pros | Glioma Grade 4 (n = 8) Grade 3 (n = 20) “Low grade” (n = 13) Meningeoma (n = 4) Metastasis (n = 2) | Mono (n = 33) Poly (n = 14) | 16.5 (mean) | Seizure free: 55.6%, ≥ 50% seizure reduction: 20% Discontinued TPM for severe side effects: 6.4% |
Valproic acid | ||||||
Van der Meer et al. (2020)c [55] | 429 | Retro | Glioma Grade 2 (n = 105) Grade 3 (n = 44) Grade 4 (n = 280) | Mono | 86.2 (median) | Treatment failure for any reason within 36-months follow-up: 56% Treatment failure because of AE within 36-months follow-up: 32% Treatment failure because of uncontrolled seizures within 36-months follow-up: 17% |
Kerkhof et al. (2013)d [7] | 36 | Retro | Glioblastoma (n = 36) | Mono | 9 (median) | Seizure free at the end of follow-up (minimum of 6 months): 77.8% |