title: Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland (A.O.R., J.N., R.S.); Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland (S.J.); Department of Neurology, Universitätspital Zürich, Zurich, Switzerland (P.R., M.W.).
authors: Andrea O
authors: AO
authors: Rossetti
authors: Sandrine
authors: S
authors: Jeckelmann
authors: Jan
authors: J
authors: Novy
authors: Patrick
authors: P
authors: Roth
authors: Michael
authors: M
authors: Weller
authors: Roger
authors: R
authors: Stupp
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000150:complications* / Q000401:mortality; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069583:Pregabalin; D011379:Prognosis; D015996:Survival Rate; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D010889:Piracetam
keywords: epilepsy; glioma; outcome; seizure; treatment