title: Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue.
abstract: BACKGROUND
  Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT.
  
  
  METHODS
  A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect.
  
  
  RESULTS
  From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80% retention and 94% self-reported compliance. There were no grade 4-5 toxicities, and the incidence of grade 2-3 toxicities was similar between treatment arms, the most common of which were anxiety and nausea (15%), headaches (19%), and insomnia (20%). There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory, Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function). However, in participants with more baseline fatigue, those treated with armodafinil did better than those who received the placebo on the end-RT assessments for several outcomes.
  
  
  CONCLUSIONS
  Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance. While there was no overall significant effect on fatigue, those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil. These data suggest that a prospective, phase III randomized trial is warranted for patients with greater baseline fatigue.
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Brandi R
authors.initials: BR
authors.lastname: Page
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Lingyi
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: David
authors.initials: D
authors.lastname: Bryant
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: David
authors.initials: D
authors.lastname: Grisell
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Lesser
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Drew C
authors.initials: DC
authors.lastname: Monitto
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Naughton
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Rapp
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Savona
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Sunjay
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Doug
authors.initials: D
authors.lastname: Case
authors.affiliation: Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D004311:Double-Blind Method; D005221:Fatigue / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D005909:Glioblastoma / Q000150:complications* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008579:Meningioma / Q000150:complications* / Q000532:radiotherapy; D008875:Middle Aged; D000077408:Modafinil; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects*; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: armodafinil; cognitive function; fatigue; primary brain tumors; radiotherapy