pregabalin and Brain-Neoplasms

In patients with brain tumors, the choice of antiepileptic medication is guided by tolerability and pharmacokinetic interactions. This study investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non-enzyme-inducing agents, in this setting.. In this pragmatic, randomized, unblinded phase II trial (NCT00629889), patients with primary brain tumors and epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability were assessed using structured questionnaires. The primary composite endpoint was the need to discontinue the study drug, add-on of a further antiepileptic treatment, or occurrence of at least 2 seizures with impaired consciousness during 1 year follow-up.. Over 40 months, 25 patients were randomized to LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue: side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor progression.. This study shows that LEV and PGB represent valuable monotherapy options in this setting, with very good antiepileptic efficacy and an acceptable tolerability profile, and provides important data for the design of a phase III trial.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Piracetam; Pregabalin; Prognosis; Survival Rate

As a member of the platinum drug group, oxaliplatin (OXAL) is used to treat brain tumors, although its use is limited through excessive calcium ion (Ca) influx and reactive oxygen species (ROS) production in neurons. The Ca permeable transient receptor potential vanilloid 1 (TRPV1) channel is activated by ROS, and its activity might be reduced by the antioxidant property of pregabalin (PREGAB). This study aimed to investigate the protective action of PREGAB against OXAL-induced oxidative neurotoxicity in human glioblastoma (DBTRG) cells. The DBTRG cells were divided into four treatment groups: control, PREGAB (500 µM for 1 h), OXAL (25 µM for 24 h), and PREGAB + OXAL. In the laser confocal microscope and plate reader analyses, apoptosis, mitochondrial membrane depolarization (JC-1), cell death (propidium iodide/Hoechst rate), and ROS-level production increased by activating TRPV1 in the cells using the OXAL treatment, although the cell viability values decreased. However, these values were recovered in the PREGAB + OXAL group using PREGAB and TRPV1 inhibitor (capsazepine) treatments. In the patch-clamp analyses, OXAL-induced TRPV1 channel activation in the OXAL group also decreased in the PREGAB + OXAL group using the PREGAB and capsazepine treatments. In conclusion, the apoptosis and oxidant actions of OXAL were increased by activation of the TRPV1 channel, but this effect was diminished by the PREGAB treatment. PREGAB treatment has the potential to be an effective strategy in the treatment of OXAL-induced oxidative neurotoxicity.

Topics: Apoptosis; Brain Neoplasms; Calcium; Caspase 3; Caspase 9; Cell Line, Tumor; Drug Interactions; Glioblastoma; Humans; Neurons; Neurotoxicity Syndromes; Oxaliplatin; Oxidative Stress; Patch-Clamp Techniques; Pregabalin; Reactive Oxygen Species; TRPV Cation Channels

There were nearly 700,000 patients in the United States in 2010 living with brain tumor diagnoses. The incidence of seizures in this population is as high as 70% and is historically difficult to control. Approximately 30-40% of brain tumors patients who present with status epilepticus (SE) will not respond to typical therapy consisting of benzodiazepines and phenytoin (PHT), resulting in patients with refractory status epilepticus (RSE). RSE is usually treated with anesthetic doses of propofol or midazolam infusions. This therapy can have significant risk, particularly in patients with cancer.. A retrospective chart review was performed on 23 patients with primary or metastatic brain tumors whose SE was treated with intravenous PHT, levetiracetam (LEV), and oral pregabalin (PGB).. In all the patients under study, PHT or LEV was used as first-line therapy. PGB was typically used as third-line treatment. The median daily dose of PGB was 375 mg (usually divided BID or TID), and the median daily dose of LEV 3000 mg (usually divided BID). Cessation of SE was seen in 16/23 (70%) after administration of PHT, LEV, and PGB. SE was aborted, on average, 24 h after addition of the third antiepileptic drug. Only one patient in the responder group required intubation. Mortality rate was zero in the responder group. No adverse reactions to this medication regimen were observed.. Our study suggests that the administration of PHT, LEV, and PGB in brain tumor patients with RSE is safe and highly effective.

Topics: Acute Disease; Aged; Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pregabalin; Retrospective Studies; Status Epilepticus; Treatment Outcome

An open pilot study to evaluate the effect of pregabalin (PGB) as add-on therapy on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy (BTRE).. We recruited 25 consecutive patients with BTRE and uncontrolled seizures. At baseline and during follow-up, patients underwent a complete physical and neurological examination and were evaluated using the QOLIE 31P (V2), EORTC QLQ C30, Adverse Events Profile, and Hamilton Anxiety Rating Scale (HAM-A). At baseline, a seizure diary was given.. During follow-up, 17 patients underwent chemotherapy, none underwent radiotherapy, 9 had disease progression, and 3 died. Mean duration of follow-up was 4.1 months. Mean PGB dosage was 279 mg/day. At baseline, mean weekly seizure frequency was 5.3 (±10) and at last available follow-up visit was 2.8±5. This difference was statistically significant (p=0.016). The responder rate was 76%. Ten patients dropped out; 4 as a result of seizure worsening, 1 as a result of unchanged seizure frequency, 3 as a result of a lack of compliance, and 2 as a result of side effects. Based on the QOLIE-31-P, a significant improvement of the subscale "seizure worry" (p=0.004) and a significant decrease in distress scores related to AEDs and social life (p=0.009 and p=0.008, respectively) were observed. A significant decrease in HAM-A score (p=0.002) was documented. CONCLUSIONS; These data indicate that PGB may represent a valid alternative as add-on treatment in this patient population, based on its efficacy on seizure control and anxiety.

Topics: Adult; Aged; Anticonvulsants; Anxiety; Benzodiazepines; Brain Neoplasms; Carbamazepine; Clobazam; Drug Therapy, Combination; Epilepsy; Female; Fructose; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenobarbital; Pilot Projects; Piracetam; Pregabalin; Quality of Life; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

Patients with brain tumors and seizures should be treated with non-enzyme-inducing antiepileptic drugs (AED). Some of the newer drugs seem particularly suited in these patients.. Here we describe our experience with pregabalin (PGB); its effectiveness was retrospectively studied in nine consecutive patients with primary brain tumors and seizures.. Six subjects had secondarily generalized and three simple partial seizures. Patients mostly suffered from WHO grade IV gliomas. PGB replaced enzyme inducing, inefficacious or bad tolerated AED, as add-on or monotherapy. Median follow-up was 5 (2-19) months; three patients died of their tumor. Daily median dosage was 300 mg. All subjects experienced at least a 50% seizure reduction, six were seizure-free. Side effects were reported in four patients, leading to PGB discontinuation in two.. PGB appears to have a promising effectiveness in this setting, even as a monotherapy. Based on these results we embarked on a prospective controlled trial.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Epilepsies, Partial; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Glioma; Humans; Male; Middle Aged; Pregabalin; Retrospective Studies; Seizures; Treatment Outcome