levetiracetam and Glioblastoma

Levetiracetam (LEV) is an anti-epileptic drug (AED) that sensitizes glioblastoma (GBM) to temozolomide (TMZ) chemotherapy by inhibiting O. A search of CINAHL, Embase, PubMed, and Web of Science from inception to May 2021 was performed to identify relevant articles. Hazard ratios (HR), median overall survival, and adverse events were pooled using random-effect models. Meta-regression, funnel plots, and the Newcastle-Ottawa Scale were utilized to identify sources of heterogeneity, bias, and statistical influence.. From 20 included studies, 5804 GBM patients underwent meta-analysis, of which 1923 (33%) were treated with LEV. Administration of LEV did not significantly improve survival in the entire patient population (HR 0.89, p = 0.094). Significant heterogeneity was observed during pooling of HRs (I. Levetiracetam treatment may not be effective for all GBM patients. Instead, LEV may be better suited for treating specific molecular profiles of GBM. Further studies are necessary to identify optimal GBM candidates for LEV.

Topics: Brain Neoplasms; Glioblastoma; Humans; Levetiracetam; Survival Analysis; Treatment Outcome

An open-label single-arm phase 2 study was conducted to evaluate the role of levetiracetam as a sensitizer of concurrent chemoradiotherapy (CCRT) for patients with newly diagnosed glioblastoma. This study aimed to determine the survival benefit of levetiracetam in conjunction with the standard treatment for glioblastoma.. Major eligibility requirements included histologically proven glioblastoma in the supratentorial region, patients 18 years or older, and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Levetiracetam was given at 1,000-2,000 mg daily in two divided doses during CCRT and adjuvant chemotherapy thereafter. The primary and the secondary endpoints were 6-month progression-free survival (6mo-PFS) and 24-month overall survival (24mo-OS), respectively. Outcomes of the study group were compared to those of an external control group.. Between July 2016 and January 2019, 76 patients were enrolled, and 73 patients were included in the final analysis. The primary and secondary outcomes were improved in the study population compared to the external control (6mo-PFS, 84.9% vs. 72.3%, p = 0.038; 24mo-OS, 58.0% vs. 39.9%, p = 0.018), but the differences were less prominent in a propensity score-matched analysis (6mo-PFS, 88.0% vs. 76.9%, p = 0.071; 24mo-OS, 57.1% vs. 38.8%, p = 0.054). In exploratory subgroup analyses, some results suggested that patients with ages under 65 years or unmethylated MGMT promoter might have a greater survival benefit from the use of levetiracetam.. The use of levetiracetam during CCRT in patients with newly diagnosed glioblastoma may result in improved outcomes, but further investigations are warranted.

Topics: Adult; Aged; Brain Neoplasms; Chemoradiotherapy; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioblastoma; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Progression-Free Survival; Propensity Score; Republic of Korea; Tumor Suppressor Proteins

Temozolomide is applied as the standard chemotherapy agent in patients with glioblastoma (GBM) after surgery. However, the benefit of this treatment for patients is limited by the invasive growth of gliomas and drug resistance. There are indications from fundamental experimental and retrospective studies that levetiracetam has the potential to improve the survival rate of patients with GBM. However, it has yet to be determined whether the combination of temozolomide and levetiracetam is more effective than standard temozolomide chemotherapy. Therefore, we designed a randomized clinical trial to investigate the therapeutic effect of the new combined regime for treating GBM.. This is a double-blind and randomized clinical trial conducted in a single center. One hundred forty-two patients will be recruited and screened for the inclusion and exclusion criteria. Then, eligible participants will be randomly assigned to an experimental group or a control group in a 1:1 ratio. Based on the administration of radiation therapy (RT), participants in the experimental group will be prescribed levetiracetam plus temozolomide chemotherapy for 34 weeks while participants in the control group will receive placebo tablets plus temozolomide for the same duration. A 3-year follow-up will be conducted on all patients after intervention. Accordingly, the primary outcome will be progression-free survival (PFS). The secondary endpoints include overall survival (OS), the Karnofsky Performance Status (KPS), the objective response rate (ORR), and adverse event incidence.. It is expected that the results of this trial will provide high-level evidence regarding the clinical benefits of levetiracetam and temozolomide combined in the treatment of GBM.. Chinese Clinical Trial Registry, ChiCTR2100049941 . Registered on 14 August 2021.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Glioblastoma; Humans; Levetiracetam; Randomized Controlled Trials as Topic; Retrospective Studies; Temozolomide

The association between levetiracetam and survival with isocitrate dehydrogenase (. In this observational single-institution cohort study (2010-2018), inclusion criteria were (1) age ≥18 years; (2) newly diagnosed supratentorial tumor; (3) histomolecular diagnosis of. A total of 460 patients were included. The median OS was longer in the 116 patients with levetiracetam use during the whole duration of the standard chemoradiation protocol (21.0 months; 95% confidence interval [CI] 17.2-24.0) than in the 126 patients with part-time levetiracetam use (16.8 months; 95% CI 12.4-19.0) and in the 218 patients who never received levetiracetam (16.0 months; 95% CI 15.5-19.4;. Levetiracetam use during the whole standard chemoradiation protocol possibly improves OS of patients with. This study provides Class III evidence that in individuals with

Topics: Adolescent; Adult; Brain Neoplasms; Cohort Studies; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Prognosis; Retrospective Studies; Survival Rate

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation; Prognosis; Retrospective Studies

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation; Prognosis; Retrospective Studies

Glioblastoma multiforme (GBM) is an aggressive brain tumor, often occurring with seizures managed with antiepileptic drugs, such as levetiracetam (LEV). This study is aimed at associating progression-free survival (PFS) and overall survival (OS) of GBM patients with LEV plasma concentration, MGMT promoter methylation, and sex. In this retrospective, non-interventional, and explorative clinical study, GBM patients underwent surgery and/or radiotherapy and received LEV during adjuvant temozolomide (TMZ) treatment. A high-performance liquid chromatography with UV-detection was used for therapeutic drug monitoring of LEV plasma concentrations. Follow-up average drug concentration was related to patients' clinical characteristics and outcomes. Forty patients (42.5 % female; mean age=54.73 ± 11.70 years) were included, and GBM MGMT methylation status was assessed. All were treated with adjuvant TMZ, and LEV for seizure control. Patients harboring methylated MGMT promoter showed a longer median PFS (460 vs. 275 days, log-rank p < 0.001). The beneficial effect of MGMT promoter methylation was more evident for females (p < 0.001) and in patients with LEV concentration ≤ 20.6 µg/mL (562 days vs. 274.5 days, p = 0.032). Female patients also showed longer OS (1220 vs. 574 days, p = 0.03). Also, higher LEV concentration (>20.6 µg/mL) synergized with MGMT promoter methylation by extending the OS (1014 vs. 406 days of patients with no methylation and low LEV average concentration, p = 0.021). Beneficial effect of higher LEV plasma levels was more evident in males (p = 0.024). Plasma concentrations of LEV may support better outcomes for chemoradiotherapy when other positive prognostic factors are lacking and may promote overall survival by synergizing with MGMT promoter methylation and male sex.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Dacarbazine; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Prognosis; Retrospective Studies; Seizures; Temozolomide; Tumor Suppressor Proteins

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation; Prognosis

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation

Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Despite new treatments developed including immunomodulation using vaccines and cell therapies, mortality remains high due to the resistance mechanisms presented by these tumor cells and the function of the blood-brain barrier that prevents the entry of most drugs. In this context of searching for new glioblastoma therapies, the study of the existing drugs to treat neurological disorder is gaining great relevance. The aim of this study was to determine, through a preliminary in vitro study on human glioblastoma (A172, LN229), anaplastic glioma (SF268) and neuroblastoma (SK-N-SH) cell lines, the possible antitumor activity of the active principles of several drugs (levomepromazine, haloperidol, lacosamide, valproic acid, levetiracetam, glatiramer acetate, fingolimod, biperiden and dextromethorphan) with the ability to cross the blood-brain barrier and that are commonly used in neurological disorders. Results showed that levetiracetam, valproic acid, and haloperidol were able to induce a relevant synergistic antitumor effect when associated with the chemotherapy currently used in clinic (temozolomide). Regarding the mechanism of action, haloperidol, valproic acid and levomepromazine caused cell death by apoptosis, while biperiden and dextromethorphan induced autophagy. Fingolimod appeared to have anoikis-related cell death. Thus, the assayed drugs which are able to cross the blood-brain barrier could represent a possibility to improve the treatment of neural tumors, though future in vivo studies and clinical trials will be necessary to validate it.

Topics: Adult; Apoptosis; Biperiden; Brain Neoplasms; Cell Line, Tumor; Dextromethorphan; Fingolimod Hydrochloride; Glioblastoma; Haloperidol; Humans; Levetiracetam; Methotrimeprazine; Valproic Acid

This study was conducted to assess whether levetiracetam (LEV) affects the survival of patients with glioblastoma (GBM) treated with concurrent temozolomide (TMZ) chemotherapy. To this end, from 2004 to 2016, 322 patients with surgically resected and pathologically confirmed isocitrate dehydrogenase (IDH)-wildtype GBM who received TMZ-based chemoradiotherapy were analysed. The patients were divided into two groups based on whether LEV was used as an anticonvulsant both at the time of surgery and the first visit thereafter. The median overall survival (OS) and progression-free survival (PFS) were compared between the groups. The OS was 21.1 and 17.5 months in the LEV (+) and LEV (-) groups, respectively (P = 0.003); the corresponding PFS was 12.3 and 11.2 months (P = 0.017). The other prognostic factors included age, extent of resection, O

Topics: Adult; Aged; Chemoradiotherapy; Disease-Free Survival; Female; Follow-Up Studies; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Retrospective Studies; Survival Rate; Temozolomide

Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported.. A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs.. To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Chorea; Female; Glioblastoma; Humans; Levetiracetam; Seizures; Spinal Cord Neoplasms

Glioblastoma multiforme (GBM) is a lethal and aggressive malignant tumor of the central nervous system. The World Health Organization classifies it as a grade IV astrocytoma. Controlling seizures is essential during GBM treatment because they are often present and closely associated with the quality of life of GBM patients. Some antiepileptic drugs (AEDs) exhibit antitumor effects and could decrease the mortality of patients with GBM. In this retrospective cohort study, we examined 418 patients treated with surgery, radiotherapy, and chemotherapy with temozolomide (TMZ) at Severance Hospital in South Korea, per the current protocol. Median overall survival (OS) was 21 months [95% confidence interval (CI): 18.1-23.9] in the levetiracetam (LEV) treatment group, whereas it was 16 months [95% CI: 14.1-17.9] in the group without LEV, exhibiting a statistically significant difference between the two groups (P < 0.001). Of nine AED groups, only LEV treatment [P = 0.001; hazard ratio (HR), 0.65; 95% CI: 0.51-0.83] exhibited a statistically significant difference in the OS, in the univariate analysis. In the risk analysis of the baseline characteristics, age, administration of LEV, and O6-methylguanine-DNA methyltransferase (MGMT) promoter status correlated with OS. The use of LEV in the group with a methylated MGMT promoter resulted in a positive impact on the OS [P = 0.006; HR, 0.174; 95% CI: 0.050-0.608], but the effect of LEV on the OS was not statistically significant in the unmethylated MGMT promoter group (P = 0.623). This study suggests that, compared with other AEDs, the administration of LEV may prolong the survival period in GBM patients with methylated MGMT promoters, who are undergoing chemotherapy with TMZ.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Child; Child, Preschool; Dose Fractionation, Radiation; Female; Follow-Up Studies; Glioblastoma; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Quality of Life; Republic of Korea; Retrospective Studies; Risk Factors; Seizures; Temozolomide; Time Factors; Treatment Outcome; Young Adult

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Glioblastoma; Hispanic or Latino; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Prospective Studies; Young Adult

Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

Topics: Aminolevulinic Acid; Anti-Inflammatory Agents; Anticonvulsants; Desipramine; Dexamethasone; Drug Therapy, Combination; Enzyme Inhibitors; Fluorescence; Glioblastoma; Humans; Levetiracetam; Phenytoin; Photosensitizing Agents; Piracetam; Protoporphyrins; Valproic Acid

Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma.. To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV).. VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use.. The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Clinical Trials as Topic; Dacarbazine; Epilepsy; Female; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prognosis; Survival Analysis; Temozolomide; Valproic Acid

Patients with grade IV astrocytoma or glioblastoma multiforme (GBM) have a median survival of <12 months, increased to 14.6 months by maximal safe resection with radiation and temozolamide. In the absence of chemotherapy, radiotherapy or chemoradiotherapy, spontaneous regression of GBM or regression while only being on dexamethasone (DEX) and levetiracetam (LEV) have seldom been reported. Here, we present a case of a patient who had significant regression of the GBM with DEX and LEV alone. In this study, we hypothesise a plausible antineoplastic role of DEX and or LEV in GBM and highlight molecular, preclinical and clinical studies supporting this role.

Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Cognition Disorders; Dacarbazine; Dexamethasone; Glioblastoma; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Regression, Spontaneous; Neoplasms, Second Primary; Piracetam; Temozolomide

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity.

Topics: Adult; Aged; Anticonvulsants; Blood Cell Count; Blood Cells; Brain Neoplasms; Chemoradiotherapy; Female; Glioblastoma; Hemoglobins; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Valproic Acid; Young Adult

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.. 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.. 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 = .010 and P = .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 = .016), MGMT promoter methylation (HR, 0.30; P = .002), and receipt of LEV (HR, 0.31; P < .001.. LEV may provide a survival benefit in patients with glioblastoma who receive temozolomide-based chemotherapy. A prospective randomized study may be indicated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chemoradiotherapy; Chemotherapy, Adjuvant; Dacarbazine; Female; Glioblastoma; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Piracetam; Proportional Hazards Models; Retrospective Studies; Temozolomide; Young Adult

Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents; Anticonvulsants; Antiemetics; Antineoplastic Agents; Dacarbazine; Dexamethasone; Drug Combinations; Erythema; gamma-Globulins; Glioblastoma; Humans; Immunologic Factors; Levetiracetam; Male; Methylprednisolone; Middle Aged; Omeprazole; Oxycodone; Piperidines; Piracetam; Proton Pump Inhibitors; Quinazolines; Stevens-Johnson Syndrome; Temozolomide; Wound Healing

To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation.. A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months. Cox-regression survival analysis was performed on 165 patients receiving chemoradiation with temozolomide of whom 108 receiving this in combination with VPA for at least 3 months.. Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on monotherapy. Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status.. Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Drug Therapy, Combination; Female; Follow-Up Studies; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Neoplasm Recurrence, Local; Piracetam; Prognosis; Retrospective Studies; Seizures; Survival Rate; Temozolomide; Valproic Acid; Young Adult

Topics: Anticonvulsants; Brain Neoplasms; Female; Glioblastoma; Humans; Levetiracetam; Male; Neoplasm Recurrence, Local; Piracetam; Seizures; Valproic Acid

Antiepileptic drugs (AEDs) are frequently used to treat seizures in glioma patients. AEDs may have an unrecognized impact in modulating O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein that has an important role in tumor cell resistance to alkylating agents. We report that levetiracetam (LEV) is the most potent MGMT inhibitor among several AEDs with diverse MGMT regulatory actions. In vitro, when used at concentrations within the human therapeutic range for seizure prophylaxis, LEV decreases MGMT protein and mRNA expression levels. Chromatin immunoprecipitation analysis reveals that LEV enhances p53 binding on the MGMT promoter by recruiting the mSin3A/histone deacetylase 1 (HDAC1) corepressor complex. However, LEV does not exert any MGMT inhibitory activity when the expression of either p53, mSin3A, or HDAC1 is abrogated. LEV inhibits malignant glioma cell proliferation and increases glioma cell sensitivity to the monofunctional alkylating agent temozolomide. In 4 newly diagnosed patients who had 2 craniotomies 7-14 days apart, prior to the initiation of any tumor-specific treatment, samples obtained before and after LEV treatment showed the inhibition of MGMT expression. Our results suggest that the choice of AED in patients with malignant gliomas may have an unrecognized impact in clinical practice and research trial design.

Topics: Anticonvulsants; Antineoplastic Agents; Blotting, Western; Cell Proliferation; Chromatin Immunoprecipitation; Dacarbazine; DNA Modification Methylases; DNA Repair Enzymes; Drug Resistance, Neoplasm; Gene Expression; Glioblastoma; Humans; Levetiracetam; Piracetam; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Temozolomide; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

Rare cases of levetiracetam-induced thrombocytopenia have been reported in the literature. We report a case of glioblastoma multiforme and partial epilepsy treated with levetiracetam with subsequent development of thrombocytopenia. After ruling out all other possible causes of a decreased platelet count, we conclude that levetiracetam was the cause of this adverse event.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsies, Partial; Female; Frontal Lobe; Glioblastoma; Humans; Levetiracetam; Middle Aged; Piracetam; Platelet Count; Thrombocytopenia; Treatment Outcome

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Topics: Anticonvulsants; Benzodiazepines; Brain Neoplasms; Cell Phone; Clobazam; Electroencephalography; Epilepsy, Complex Partial; Female; Frontal Lobe; Glioblastoma; Humans; Levetiracetam; Magnetic Resonance Imaging; Middle Aged; Piracetam; Status Epilepticus; Tomography, X-Ray Computed

Topics: Age Factors; Anticonvulsants; Antiemetics; Antineoplastic Agents; Brain Neoplasms; Glioblastoma; Humans; Levetiracetam; Logistic Models; Nausea; Piracetam; Retrospective Studies; Vomiting