Table 1 A summary of the evidence regarding the potential benefit of pharmacologic intervention in cancer patients with cognitive impairment and fatigue

MODAFINIL

Thought to inhibit GABA outflow tracts within the ventro-lateral preoptic area of the hypothalamus.

Clinical trials have looked at fatigue as a primary outcome and cognition as a secondary one, although most have demonstrated efficacy in improving cognition.

METHYLPHENIDATE

Dopaminergic and noradrenergic agonist which acts to increase levels of these neurotransmitters within the frontal striatal network.

Randomised, double-blind trials in childhood cancer patients suggest efficacy, but no evidence of superiority over placebo in adult trials.

DONEPEZIL

Centrally acting anticholinergic used in the management of Alzheimer’s Disease.

Open-label Phase II studies in glioma patients suggested statistically significant improvement in cognitive functioning.

LITHIUM

Cation with an unknown mechanism of action used in the management of bipolar mood disorder.

Murine models and efficacy data from bipolar patients suggest anti-apoptotic and neuroprotective potential.

PPARs

Nuclear hormone receptor functioning as a transcription factor, targeted in the control of type II diabetes mellitus.

Murine models have demonstrated protection against radiation induced cognitive dysfunction.

ARBs

Antagonism of the angiotensin II receptor used in the management of hypertension.

Murine models have demonstrated protection against radiation induced cognitive dysfunction.

NOS

Produces NO which functions as a neurotransmitter.

None, theoretical benefit through induction of NOS and subsequent antioxidant activities.

MEMANTINE

NMDA antagonist used in the management of Alzheimer’s Disease.

Recent randomised placebo-controlled double-blind trial in patients receiving whole brain radiation showed longer time to cognitive decline over placebo.

N-ACETYL CYSTEINE

Provides cysteine, the rate limiting step in the synthesis of the anti-oxidant glutathione.

Limited evidence of efficacy in Phase II trials in Alzheimer’s patients.

RESVERATROL

Unknown, demonstrates anti-apoptotic and anti-oxidant properties within cell cultures.

Phase II studies in Alzheimer’s patients suggest little to no cognitive benefit.

NSAIDS

Inhibition of COX isoforms.

Recent Cochrane review indicates no significant impact in slowing cognitive decline in Alzheimer’s patients, Women’s Health study subanalysis echoes this finding.