The cognitive effects of modafinil in breast cancer survivors: A randomized clinical trial
Reviewer: Christine Hill, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 3, 2007
Presenter: Kohli, S. Presenter's Affiliation: University of Rochester, Rochester, NY Type of Session: Scientific
As the number of cancer survivors continues to increase, after-effects of cancer and its treatments have become increasingly important. Cognitive changes and impairment after cancer treatment, often referred to as "chemo-brain" or "chemo-fog", is of great concern to patients and physicians.
In a previous study by the presenting authors of 94 breast cancer patients, 82% reported cognitive changes after completing cancer treatment (Jean-Pierre P, J Support Onc, 2006).
Traditional stimulants have shown some efficacy in treatment of cognitive and attention deficits after cancer treatment; however, these drugs are associated with significant side-effects.
Modafinil (Provigil) is a wakefulness-promoting agent that is approved by the Food and Drug Administration for treatment of narcolepsy.
Modafinil is felt to carry a very low risk of dependency and side effects, and has been demonstrated to improve working memory and attention for military workers required to perform continuous tasks.
This study was carried out to evaluate the role of modafinil in treatment of cancer-related cognitive impairment.
Materials and Methods
This study enrolled female breast cancer patients who had completed chemotherapy at least one month prior to enrollment, and reported a score of at least 2 on the Brief Fatigue Inventory (BFI).
The trial was conducted in two phases: In Phase 1, all patients were treated with modafinil, 200 mg daily, open-label, for four weeks. Patients with a positive response to modafinil with regards to fatigue went on to Phase 2. In Phase 2, patients were randomized to placebo or an additional four weeks of modafinil (200 mg daily).
Attention and memory were assessed via the Cognitive Drug Research Computer-Based Neuropsychiatric Assessment (CDR) at baseline, after Phase 1, and after Phase 2.
The trial was originally designed to measure fatigue as its primary endpoint; cognitive effects were assessed as a secondary endpoint, and are reported here.
82 patients were enrolled on the trial, with a mean age of 54 years (range 33-83 years). The average time since completion of chemotherapy was 22.8 months prior to enrollment.
Six patients self-discontinued the study medicine during Phase 1 due to side effects of anxiety, headache, and nausea, which have been previously reported with modafinil use. An additional 8 patients did not experience any improvement in fatigue after Phase 1 and were thus not eligible for Phase 2. A total of 68 patients were randomized in Phase 2.
A statistically significant improvement in fatigue was demonstrated after Phase 1 when compared to baseline (p < 0.001), accompanied by a 45% decrease in disturbed sleep symptoms.
Significant improvements based on CDR were also noted in episodic memory and speed of memory after Phase 1 when compared to baseline (p < 0.001, p = 0.0073, respectively). No significant effect on working memory or power of attention was demonstrated after Phase 1 when compared to baseline CDR.
At the end of Phase 2, the modafinil group demonstrated improved continuity of attention as compared to placebo (p = 0.002), as well as improved episodic memory (p < 0.005), speed of memory (p = 0.009), picture recall (p = 0.02) and word recall (p = 0.03).
Modafinil provides significant improvement in attention and speed of memory for breast cancer patients following cancer treatment.
Modafinil may enhance quality of life in this patient population.
The authors note the following limitations to this study: Firstly, the majority of patients enrolled on the study were both Caucasian and highly educated, so results may or may not be generalizable. Secondly, the trial was designed to evaluate the effects of modafinil on fatigue, the primary study endpoint. Within this abstract, findings with regards to cognitive effects, a secondary endpoint, are reported.
Complaints of cognitive impairment after cancer treatment are common, particularly after breast cancer treatment.
This study indicates significant improvement in memory and attention in breast cancer patients with treatment with modafinil after completion of cancer treatment.
Cancer survivors may suffer from depression, anxiety, and fatigue after treatment, all of which can contribute to "chemo-brain". However, previous studies have suggested that cognitive impairment after chemotherapy is independent of these other symptoms. With use of modafinil, separating effect on cognition from the confounding factor of improved wakefulness may prove to be difficult. Even so, improved attention and memory with use of modafinil may contribute substantially to improvement in quality of life.
Findings with regards to fatigue after Phase 2 of this trial (modafinil versus placebo) are not reported here; however, these results may well further support the use of modafinil in this population.
Although Phase 2 of this trial was indeed randomized, the Phase 1, open-label component provides a potential for increased placebo effect in Phase 2. Further investigation of modafinil in a randomized controlled trial would be warranted in the future.
Nov 2, 2010 - Most recent oncology randomized controlled trials evaluate drugs that are available "off-protocol therapy" in the United States, and this can adversely impact trial enrollment, according to a study published online Oct. 25 in the Journal of Clinical Oncology.