Except for chemotherapy-induced anemia, the mechanisms responsible for fatigue in people with cancer are not known. Understanding the causes of fatigue in people with cancer is especially challenging because each individual may experience multiple possible causes of fatigue simultaneously. This multifactorial etiologic hypothesis is apparent in the various models that have been proposed for the study of fatigue.[1,2] Energy balance, stress, life demands, sleep, neurophysiologic changes, disruption of circadian rhythms, cardiac issues, and neuroimmunologic changes are generally incorporated in these models, based on the rationale that these factors are associated with fatigue in contexts other than cancer. The cancer literature supports some of these variables.
There is a burgeoning amount of evidence, particularly in women with breast cancer and men with prostate cancer, that fatigue is associated with markers of increased immune inflammatory activity. When fatigued individuals with a history of breast cancer are compared with breast cancer survivors without fatigue, different patterns emerge with respect to interleukin-6, interleukin-1 receptor antagonist, C-reactive protein, neopterin, and soluble tumor necrosis factor receptor-II.[4,5,6] Although the precise relationships-and the clinical meaning of those relationships-are not yet known, increased cytokines likely contribute to the symptoms of asthenia, fatigue, and lethargy, as supported in animal models of cytokine-induced sickness behavior [7,8] and in humans. There have not yet been large, well-controlled studies that have evaluated the effects of general anti-inflammatory agents on fatigue or cytokine biomarkers.
Palliative care helps relieve symptoms that bother the patient and helps improve the patient's quality of life.
The goal of palliative care is to improve the quality of life of patients who have a serious or life-threatening disease. Palliative care is meant to prevent or treat symptoms, side effects, and psychological, social, and spiritual problems caused by a disease or its treatment.
Palliative care for patients with advanced cancer includes nutrition therapy (see the Treatment of Symptoms...
Other studies demonstrate a change in the regulation of cortisol by the hypothalamic pituitary adrenal axis. One key study put fatigued and nonfatigued breast cancer survivors through a stress battery in a laboratory setting. Nonfatigued survivors mounted a significant cortisol increase in response to acute stress, while fatigued survivors had a very blunted response. Another study has shown fatigued breast cancer survivors have flattened cortisol slopes, having higher levels of cortisol at the end of the day than do nonfatigued survivors. It is the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis that may account for the prolonged inflammatory cytokine milieu; understanding the body's response to numerous chronic stressors in cancer may help in managing fatigue.
Finally, another theory is that serotonin is negatively impacted through chronic exposure to proinflammatory cytokines. One hypothesis is that the relationship between central nervous system concentrations of serotonin and fatigue have a U-shaped relationship, suggesting that very high and very low levels of serotonin may be associated with cancer-related fatigue. However, studies that have evaluated serotonergic agents have not demonstrated a benefit for fatigue. The role and relationship of many important neurotransmitters such as dopamine, norepinephrine, and serotonin with HPA axis functioning and cytokine expression have yet to be fully understood.
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Eisenberger NI, Inagaki TK, Mashal NM, et al.: Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun 24 (4): 558-63, 2010.
Bower JE, Ganz PA, Aziz N: Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue. Psychosom Med 67 (2): 277-80, 2005 Mar-Apr.
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