Aiming for a Better Understanding and Management of Cancer-Related Fatigue

Abstract

Cancer-related fatigue (CRF) is a serious symptom of patients with cancer and deteriorates their daily quality of life. Whereas fatigue is a common problem in the general population, with a prevalence of about 30%, up to 99% of patients with cancer have fatigue of more intense severity. CRF is directly related to the biology of cancer, but it can also be caused by anticancer treatment. We reviewed current evidence about the potential pathophysiological mechanisms causing CRF. Clinical methods to determine the presence and severity of CRF and potential treatment options to reduce CRF will be discussed. After reading this review, the reader will have knowledge of the current understanding of CRF and will be able to give evidence-based advice to patients with CRF. The Oncologist 2013;18:1135-1143Implications for Practice: Cancer-related fatigue (CRF) is a common problem in patients with cancer and has a major impact on quality of life. The causes of CRF are multifactorial and not fully understood. To get a better insight into the underlying mechanisms and the potential treatment possibilities of CRF, we provide an overview of currently available literature on this subject. Because current treatment options other than antitumor therapy for some of the patients are scarce and only directed at symptoms, further investigation of CRF is warranted to develop rational treatment options.

Muscle mass as a target to reduce fatigue in patients with advanced cancer

“…In the current study, the effect of pain and distress, which can also influence fatigue scores,1 was not evaluated. Furthermore, central aspects of CRF, such as the effect of serotonin and cortisol levels on the functioning of the suprachiasmatic nucleus, may play a major role in its severity, independent from their effect on muscle mass 4. The positive effect of endurance exercise on CRF may be related to these central effects 6.…”

“…Cancer‐related fatigue is one of the most prevalent symptoms experienced by patients with cancer, both during and after treatment 2, 3. Although advances are being made, the aetiology of CRF is not yet fully understood, and treatment is mostly symptomatic 4, 5. The pathophysiology of CRF is determined by central and peripheral aspects of fatigue 4, 6, 7.…”

“…Central effects of elevated cytokine levels (among which interleukin‐2, interleukin‐6, and tumour necrosis factor alpha) cause changes in activity of the hypothalamus‐pituitary‐adrenal axis, leading to a sensation of reduced capacity to perform physical work, but also to a reduced androgen expression 6, 8. Both pathways could result in a loss of muscle mass, but whether a decreased muscle mass itself affects CRF is unclear 4, 9…”

“…Which type of exercise (e.g. aerobic, resistance), and at which intensity level, contributes most to the positive effect on CRF is not yet fully known4, 12, 13 and neither is the pathophysiological mechanism of this effect. Several studies have been performed investigating the effect of exercise interventions on CRF in patients with limited disease, and their results indicate improvement of CRF and increased muscle mass, but the effect sizes varied 14, 15, 16, 17, 18.…”

Cancer-related fatigue shows a stable association with diurnal cortisol dysregulation in breast cancer patients

“…Moreover, the 24h-circadian rhythm is regulated by the suprachiasmatic nucleus (SCN) in the hypothalamus through release of melatonin and the diurnal cortisol curve. Hence, alterations of the diurnal cortisol pattern may lead to disruption of this circadian rhythm which have shown negative effects on sleep pattern and sleep quality and have been found to be associated with fatigue [37][38][39].…”