title: A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors.
abstract: OBJECTIVE
  Seizures are a potentially devastating complication of resection of brain tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas.
  
  
  METHODS
  Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned.
  
  
  RESULTS
  The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of 0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients.
  
  
  CONCLUSIONS
  The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%-18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Adam S
authors: AS
authors: Wu
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Victoria T
authors: VT
authors: Trinh
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Dima
authors: D
authors: Suki
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Susan
authors: S
authors: Graham
authors: Neuro-Oncology The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Arthur
authors: A
authors: Forman
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Jeffrey S
authors: JS
authors: Weinberg
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Ian E
authors: IE
authors: McCutcheon
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Sujit S
authors: SS
authors: Prabhu
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Amy B
authors: AB
authors: Heimberger
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Raymond
authors: R
authors: Sawaya
authors: Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Xuemei
authors: X
authors: Wang
authors: Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Wei
authors: W
authors: Qiao
authors: Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Kenneth
authors: K
authors: Hess
authors: The Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Frederick F
authors: FF
authors: Lang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D001499:Bayes Theorem; D001932:Brain Neoplasms / Q000601:surgery*; D003399:Craniotomy; D005260:Female; D005910:Glioma / Q000601:surgery; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D010672:Phenytoin / Q000627:therapeutic use*; D011446:Prospective Studies; D012640:Seizures / Q000453:epidemiology* / Q000517:prevention & control*; D015173:Supratentorial Neoplasms / Q000601:surgery; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin
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