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

The primary aim was to evaluate the safety and efficacy of modafinil in improving cancer-related fatigue (CRF) in patients with cancer.

The secondary aim was to assess the effect of modafinil on depression, quality of life (QOL), functional status, and cognitive function.

After initial assessment for all outcome measures, patients were treated with self-administered modafinil at an initial dose of 100 mg per day during weeks one to two. During weeks three to four, the dose was increased to 200 mg per day. All study parameters were reassessed at week two and at week four (completion of the trial).

• Twenty-seven patients were enrolled, and 19 completed the study.
• Average age was 60 years.
• Of the participants, 37% were male and 63% were female.
• Eastern Cooperative Oncology Group (ECOG) Performance: ECOG 1 was 37%; ECOG 2 was 44%; and ECOG 3 was 19%.

This was an open-label pilot study.

• Primary Aim: Brief Fatigue Inventory (BFI)–Fatigue
• Secondary Aim
  • Cognitive Measures
    • Hopkins Verbal Learning Test (HVLT)—assessed verbal learning and memory
    • Grooved Pegboard Test—fine motor ability and hand-eye coordination
    • Controlled Oral Word Association Test (COWAT)—verbal fluency
    • Trail Making Test (TMT) Parts A & B—visual attention, motor speed, and cognitive flexibility
  • Other Measures
    • Hospital Anxiety and Depression Scale (HADS)—depression
    • Functional Assessment of Cancer Therapy-Brain (FACT-BR)—QOL
    • Barthel Index—functional status
    • ECOG—performance status
    • National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 2.0––scored severity of detected side effects

BFI was improved at two weeks for 46% of participants, and at four weeks, 75% had a significantly improved score (p = 0.025). FACT-BR showed an improvement in all subsets of well-being except social/family at two and four weeks (p < 0.05). HADS score declined significantly at two and four weeks (p < 0.001). Cognitive function was not significantly changed, except TMT-B showed a trend for an overall improvement. Functional status (Barthel Index) did not change, but overall performance status (ECOG) improved, with 40% of patients improving at least one level. Most side effects were mild. Side effects seen were dizziness, nausea, diarrhea, and heartburn.

Modafinil use was associated with improvement in fatigue, depression, and QOL measures and was well tolerated.

• The study had a small sample size, with an almost 30% drop-out rate.
• The study was an open-label design pilot study.
• No control comparison was included.