Pilot study of modafinil for treatment of neurobehavioral dysfunction and fatigue in adult patients with brain tumors.

1503 Background: Patients with brain cancer develop neurobehavioral dysfunction and fatigue that compromise their performance of daily activities. We report results from evaluating the efficacy and safety of modafinil treatment for tumor/therapy sequelae in this medically fragile patient population. METHODS Patients: 21-65 years old with primary malignant disease or nonmalignant cerebral tumors treated with neurosurgical resection, radiotherapy, and/or chemotherapy. Clinical Global Impression of Severity ratings of mild to severe attention/memory impairment and/or fatigue. MEASURES Trail Making (TM) A and B, Symbol Digit Modalities (SDM), Verbal Fluency (VF), Hamilton Depression Scale (HAM-D), Fatigue Severity Scale (FSS), Visual Analogue Fatigue Scale (VAFS), Modified Fatigue Impact Scale (MFIS). DESIGN Double-blind dose-controlled randomization (200 or 400 mg/day modafinil in divided doses) 3 wks; Washout 1wk; Open label extension 8 wks. STATISTICAL ANALYSES Changes from baseline at scheduled visits (1, 3, 4, 8, 12 wks) using paired t-tests or Wilcoxon Signed Rank tests as appropriate. RESULTS Thirty patients, 63% male, mean age (SD) = 45.3 (11.7) yrs were accrued from 6/03-10/05. Illness severity: moderate 3 (10%), marked 13 (43%), severe 14 (47%). Tumor histology: glioblastoma multiforme 8 (27%), anaplastic glioma 10 (33%), low grade glioma 10 (33%), meningioma 1 (3%), CNS lymphoma 1 (3%). TREATMENT neurosurgical resection 93%, radiotherapy 87%, chemotherapy 70%. The table shows relationships of nine variables at baseline and 8 and 12 weeks after initiation of modafinil. Adverse events reported by ≥4 patients: headache 13 (42%); insomnia 8 (26%); dizziness 7 (23%); dry mouth 7 (23%); depressed consciousness 5 (16%); nausea 4 (13%). CONCLUSIONS Results show improvement across cognitive, mood, and fatigue outcome measures. Modafinil was generally well tolerated, with a low incidence of adverse events. Greatest improvements in outcomes were observed 8 wks after baseline. [Table: see text] [Table: see text].