Cancer-related Fatigue

Prevalence, Assessment and Treatment Strategies

Joachim Weis


Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(4):441-446. 

In This Article

Factors Associated With Fatigue

Currently, in most publications, fatigue is understood as a multidimensional construct, focusing not only on biochemical or pathophysiological factors, but also involving psychological and behavioral aspects.[14,101]

Fatigue can be caused either by cancer or its treatment. Several studies reveal high correlations of tumor-specific treatment and fatigue symptoms, or emphasize that fatigue is commonly increased during treatment and decreases after the end of treatment.[15,16] However, there are also some studies that show fatigue to be a continuous problem in aftercare, especially immediately after allogeneic hematopoietic stem cell transplantation or sometimes after primary treatment has ended.[17] There is also some evidence that the level of fatigue among cancer patients, as well as in long-term survivors several years after diagnosis, is higher than among the normal population.

Although there has been a lot of research within the last decade, there is only limited evidence for a comprehensive theory explaining the causes of fatigue. Numerous factors are being discussed to influence CRF, including medical conditions, biochemical and psychological factors, and particularly mood disturbances. Proposed mechanisms are proinflammatory cytokines, dysregulation of the hypothalamic–pituitary–adrenal axis, desynchronization of circadian rhythm, skeletal muscle wasting and genetic dysregulation.[18–22] Within the somatic perspective, a variety of factors are discussed, including states of oxygen insufficiency, metabolism disorders, hormone imbalance and blood modifications (anemia, hypokalemia or hypocalcemia).[23] Extremely high fatigue levels are correlated with specific forms of cancer treatment, such as IFN-α or interleukin therapy.[24]

There is also a strong correlation of fatigue with sleeping disorders, which may represent a potential secondary cause of fatigue.[25,26] Studies on psychological factors focus on the correlation between CRF and psychiatric comorbidity, especially depression and anxiety.[27–29] As fatigue is a common symptom of depression and is often associated with anxiety, diagnostic efforts that reliably differentiate CRF from depression are required.[30–32] One possible explanation for the continuing level of depression and anxiety is given by the fact that the perception of feelings that cancer is a life-threatening illness, as well as the distress of the treatment, may cause a physical and emotional exhaustion. Nevertheless the interaction between fatigue and depression or anxiety is not yet completely understood.[21,24] Long-term fatigue has also been interpreted as a psychological maladaptation to the sequelae of cancer.[33] Only a few studies investigate the complexity of interactions between the physical and psychological aspects of CRF.[34]

Cancer-related fatigue does not only affect the individual patient and his or her spouse, but also has a lot of consequences on the health economy. Patients complaining of CRF show a higher rate of the demand for physician counseling, private practitioner support or other health services and higher rates of sick leave and loss of work capacity.[12,14,35] Moreover, CRF has been proven to be a negative predictor for return to work after cancer.[36]


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