A RANDOMIZED, BLINDED, PLACEBO-CONTROLLED TRIAL OF DIVALPROEX SODIUM PROPHYLAXIS IN ADULTS WITH NEWLY-DIAGNOSED BRAIN-TUMORS

Background: Seizures occur after the diagnosis of brain tumors in up t o 40% of patients. Prophylactic anticonvulsants are widely advocated d espite a lack of convincing evidence of their efficacy in preventing f irst seizures. We conducted a randomized, double-blind, placebo-contro lled study comparing the incidence of first seizures in divalproex sod ium- and placebo-treated patients with newly diagnosed brain tumors. P atients and Methods: Patients who had not previously had a seizure wer e randomized within 14 days of diagnosis of their brain tumor to recei ve either divalproex sodium or placebo. All patients had at least one supratentorial brain lesion, a Karnofsky Performance Score (KPS) great er than or equal to 50%, and no previous anticonvulsant use or other b rain disease. Compliance and adequacy of dosing were assessed by pill counts and monthly blood levels. Results: Seventy-four of 75 consecuti ve eligible patients were entered in this study. Median follow-up was 7 months. The drug and placebo groups did not differ significantly in age, sex, KPS, primary tumor type, number or location of brain lesions , frequency of brain surgery, or pretreatment EEG. Thirteen of 37 pati ents (35%) receiving divalproex sodium and 9 of 37 patients (24%) on p lacebo had seizures. The odds ratio for a seizure in the divalproex so dium arm relative to the placebo arm was 1.7 (95% CI 0.6 to 4.6; p = 0 .3). The hypothesis that anticonvulsant prophylaxis provides a reducti on in the frequency of first seizure as small as 30% was rejected (p = 0.05). Conclusions: Anticonvulsant prophylaxis with divalproex sodium is not indicated for patients with brain tumors who have not had seiz ures.