Following cancer treatment, some breast cancer survivors report cognitive impairment, which has commonly been attributed to the receipt of chemotherapy and colloquially termed “chemobrain” (1
). Cognitive deficits identified by cancer survivors consist of a range of difficulties including memory and concentration problems that can emerge during cancer treatment and continue to have long-term effects for many months and years after its completion (2
). Impairment of brain function profoundly affects cognition, psychological well-being, and the ability to perform the usual activities of daily living.
Changes in cognitive function may be confused with or confounded by other problems commonly associated with cancer and its treatment, such as depression, anxiety, and fatigue caused by sleep deprivation (9
). Although the phenomenon is not understood completely, cognitive deficits in cancer patients are assuming greater significance as cancer survival improves. Advances in basic sciences, imaging, and clinical sciences are beginning to unravel pathophysiologic mechanisms which may underlie this problem (12
). Pharmacologic treatment options for cognitive deficits in cancer survivors are borrowed from diverse diseases including attention-deficit/hyperactivity disorder and neurodegenerative diseases (13
). Conventional therapies soon may find new applications; for example, recent preclinical data suggest that modafinil (Provigil®) may have some cognitive-enhancing abilities, which may positively affect patients who experience “chemobrain”.
Modafinil is a novel wake-promoting agent that is effective and well tolerated in the treatment of excessive sleepiness associated with narcolepsy and in persons with shift-work sleep disorder (15
). The precise mechanism(s) through which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions like those of sympathomimetic agents including amphetamine and methylphenidate, although the pharmacologic profile of modafinil is not identical to that of the sympathomimetic amines. The recommended single daily dose range for narcolepsy is 100-400mg modafinil (Provigil®). These doses have wake-promoting efficacy comparable to 20-40mg doses of methylphenidate (20
), which has been used previously in cognitive studies in patients with advanced cancer (21
We completed a study examining the effect of modafinil on fatigue and sleep complaints in 82 breast cancer patients following completion of chemotherapy (22
). Patients received 200 mg modafinil once daily for one month. Of the 82 women enrolled, 76 completed the study and began the study medication. A majority, 68 of the 76 women (90%) who completed the one-month study, reported improvement on all four measures of fatigue used (23
), all p < 0.001 (). In addition, the Epworth Sleepiness Scale showed a 22% decrease (p < 0.01), and the “disturbed sleep” symptom on the symptom inventory (27
) decreased more than 45% (p < 0.01).
Figure 1 Fatigue levels in post-treatment breast cancer patients receiving open-label modafinil (22).
Despite these findings, little is known about the causes of cognitive changes seen during and after cancer treatment. It seems reasonable to assume that they are related, at least in part, to other psychological and biological treatment complaints such as fatigue, sleeping problems and depression (10
). The nature of the relationships among these variables, however, both at onset and over time remains unclear.
To our knowledge, in spite of evidence that modafinil acts as a cognitive enhancer in healthy subjects (29
), no study to date has examined the effect of modafinil on a wide range of cognitive functions using a comprehensive and well-validated neuropsychological test battery in cancer patients. Therefore, as modafinil was effective in reducing persistent fatigue in our primary study (22
), we conducted secondary analyses to assess the effect of modafinil on cognitive function and to examine whether modafinil might act as a cognitive enhancer in breast cancer patients who have completed treatment for cancer.