Page, B.R., Shaw, E.G., Lu, L., Bryant, D., Grisell, D., Lesser, G.J., . . . Shah, S. (2015). Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue. Neuro-Oncology, 17, 1393–1401. 

Patients were randomized to receive a placebo or 150 mg per day dose of armodafinil. Armodafinil was taken daily during seven weeks of radiation therapy and then an additional four weeks. There were no dose modifications or drug holidays. If patients could not tolerate the study agent, it was discontinued. Fatigue, cognitive function, and quality of life were assessed at baseline, at the end of RT, and four weeks after RT. Toxicities were evaluated weekly.

• N = 54
• MEDIAN AGE = 59 years (range = 20–79 years)
• MALES: 46%, FEMALES: 54%
• KEY DISEASE CHARACTERISTICS: All patients had brain tumors and were receiving brain irradiation.

• SITE: Multi-site
• SETTING TYPE: Not specified
• LOCATION: North Carolina

PHASE OF CARE: Active antitumor treatment

Double blinded, placebo-controlled, randomized, controlled trial (n = 26 [armodafinil], n = 28 [control])

• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) subscale
• Brief Fatigue Inventory (BFI)
• Epworth Sleepiness Scale (ESS)
• Functional Assessment of Cancer Therapy–Brain (FACT-B) scale
• Verbal fluency category test
• Hopkins Verbal Learning Test–Revised (HVLT-R)
• Trail Making Test (TMT) parts A and B
• Backwards Digit Span Test

Nine patients dropped out of the study by the end of RT. The most common adverse effects were headache, insomnia, nausea, anxiety, arthralgia, dizziness, dry mouth, sinusitis, and throat and respiratory infections. There were no significant differences in adverse events between the study groups. There were no significant differences between groups in fatigue. In both groups, fatigue increased during treatment and improved following the completion of RT. Neurocognitive measures improved slightly over time in both groups with no significant difference between the groups. Among patients with the most fatigue at baseline, those taking armodafinil showed improvements in fatigue at the end of RT. Armodafinil also did not improve neurocognitive outcomes at the end of RT or at four weeks post RT in the subsets of participants with high or low levels of fatigue at baseline.

Armodafinil was not shown to improve fatigue or cognitive function measures in patients receiving brain irradiation. Armodafinil appeared to show some benefit in improving fatigue among those with high levels of fatigue at baseline.

• Small sample (< 100)
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: The size of the final sample was underpowered. No intent to treat analysis was described. The sample was limited to patients receiving brain irradiation.

The findings did not provide overall support for effectiveness of armodafinil to reduce fatigue in this study although patients with the highest level of fatigue at baseline appeared to have some benefit. Additional research is warranted to determine if there is any benefit of psychostimulants for fatigue and cognitive impairment in patients with brain tumors undergoing radiation therapy.