Blackwell, L., Petroni, G., Shu, J., Baum, L., & Farace, E. (2009). A pilot study evaluating the safety and efficacy of modafinil for cancer-related fatigue. Journal of Palliative Medicine, 12, 433–439.

The study's primary aim was to evaluate the safety and efficacy of modafinil in improving cancer-related fatigue. Its secondary aim was to determine the effect of modafinil on depression, quality of life, functional status, and cognitive function.

Participants were given 100 mg of modafinil daily for weeks 1 and 2, and then 200 mg daily for weeks 3 and 4. Participants older than 80 were dose-reduced and received 50 mg of modafinil daily for weeks 1 and 2, then 100 mg daily for weeks 3 and 4. There was no control group.

Testing was completed at baseline, week 2, and at the completion of the trial. 

• The total number of participants was 27, with 19 completing the study.
• The average participant age was 60 years.
• 63% of participants were female and 37% were male.
• 37% of participants had an Eastern Cooperative Oncology Group (ECOG) score of 1, 44% had a score of 2, and 19% had a score of 3. 

This was a prospective, open-label pilot study.

• The Hopkins Verbal Learning Test (HVLT) assessed verbal learning and memory.
• The Grooved Pegboard Test assessed fine motor ability and hand-eye coordination.
• The Controlled Oral Word Association Test (COWAT) assessed verbal fluency.
• The Trailmaking Test, Parts A and B (TMT-A & B) assessed visual attention, motor speed, and cognitive flexibility.
• The Brief Fatigue Inventory (BFI) assessed fatigue.
• The Hospital Anxiety and Depression Scale (HADS) assessed depression.
• The Functional Assessment of Cancer Therapy-Brain (FACT-BR) assessed cancer-related quality of life for patients with brain tumors
• The Barthel Index assessed functional status.
• The Eastern Cooperative Oncology Group (ECOG) performance status measured general well-being; scores range from 0 (indicating perfect health with no restriction of activities) to 5 (indicating death). 
• The National Cancer Institute Common Toxicity Criteria (CTC), Version 2.0 scored the severity of detected side effects.

Fatigue (as measured by the BFI) was improved at week 2 for 46% of participants; at week 4, 75% had a significantly improved score (p = 0.025). Functioning (as measured by the FACT-BR) showed an improvement in all subsets of well-being at weeks 2 and 4 (p < 0.05) except social/family. Depression (as measured by the HADS) declined significantly at weeks 2 and 4 (p < 0.001). 

Functional status (as measured by the Barthel Index) did not change, but overall ECOG performance status improved, with 40% of patients improving at least one level. Cognitive function was not significantly changed, although the TMT-B did show a trend of overall improvement. 

Modafinil did not significantly improve learning and memory, fine motor ability, verbal fluency, or executive function, but results are limited due to the small sample size.

• This was a pilot study addressing fatigue, with cognitive function measured as a secondary outcome.
• The study had a small number of participants, with a drop-out ratio of 30%.
• The study had an open-label design.
• There was no control group. 
• Results for improvement on the TMT-B may be due to Type I error, given the multiple tests (multiple comparisons) examined in this trial.
• The study had limited cognitive assessment.
• The issue of practice effects was not addressed in a repeated measures study.