Kohli, S., Fisher, S.G., Tra, Y., Adams, M.J., Mapstone, M.E., Wesnes, K.A., … Morrow, G.R. (2009). The effect of modafinil on cognitive function in breast cancer survivors. Cancer, 115(12), 2605–2616.

The study's primary aim was to examine the effect of modafinil on persistent fatigue after treatment. Its secondary aim was to examine the effect of modafinil on cognitive function of patients with breast cancer.

In phase 1, participants were given 200 mg of modafinil daily for four weeks. Participants with a positive response in phase 1 were randomized to phase 2. In phase 2, participants continued to receive 200 mg of modafinil orally once per day or a placebo for four weeks. Repeated measures were completed at baseline (week 0), week 4, and week 8. Participants were stratified by treatment type: chemotherapy, radiation, or both chemotherapy and radiation. 

• The total number of participants was 82, with 76 completing phase 1 and 68 completing phases 1 and 2.
• The median participant age was 54, with a range of 33–83.
• All participants were female.
• All participants had breast cancer and were being treated with surgery and chemotherapy; 87% also received radiation.
• 75% of participants had at least some college education.

The study took place at the University of Rochester Medical Oncology Clinic in New York. 

The study was a prospective, open-label clinical trial.

• The Cognitive Drug Research (CDR) assesses domains of attention and memory, including speed of memory, continuity of attention, quality of episodic and working memory, and power of attention.
• The Brief Fatigue Inventory (BFI) assess fatigue.

Approximately 70% of the participants in the active treatment group had an improvement in continuity of attention from baseline to after treatment (week 8), compared with 52% in the placebo group; however, this difference was not statistically significant (p = 0.19).

In phase 1, modafinil had a significant effect on speed of memory (p = 0.0073) and quality of episodic memory (p = 0.0001). No significant effect in continuity of attention, quality of working memory, or power of attention was observed during this phase.

In phase 2, those who continued modafinil demonstrated significantly greater improvement in cumulative speed of memory (p = 0.029), quality of episodic memory (p = 0.0151), and continuity of attention (p = 0.0101).

Modafinil significantly improved some cognitive functioning, including speed of memory and episodic memory, but failed to demonstrate improvement in working memory.

• Findings were a secondary analysis; cognitive functioning was not the study's primary outcome.
• The study was an open-label trial, and thus participants were not blinded to their assignment.
• The study had a relatively small sample size.
• The majority of participants were an educated group of Caucasian women, limiting generalizability.
• The study did not report if differences existed between the original enrolled sample (n = 82) and those who completed the entire study (n = 68).
• Although not statistically significant, the participants assigned to the modafinil group had a mean age which was five years younger than the placebo group.
• Although the Cognitive Drug Research has been used reliably in other populations, it does not indicate if it has been used in cancer populations.