Fatigue has long been recognized as a common symptom of cancer, cancer therapy, and human immunodeficiency virus (HIV) infection. Like pain, fatigue is a subjective sensation. Although there is no universal definition of fatigue, it is generally characterized by a feeling of debilitating tiredness or loss of energy, weakness, exhaustion, lethargy, malaise, or asthenia. In patients with cancer or HIV infection, fatigue is a frequent but inadequately studied and poorly understood symptom.[1-5] In addition to the fatigue experienced by cancer patients during the course of their disease and its treatment, significant degrees of fatigue may persist in survivors for years after treatment ends, even when all known causes have been resolved and the patients are in remission.[6,7] In patients with HIV infection, significant fatigue accompanies the acute infection but becomes a prominent persistent symptom as the disease progresses to acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. In both patient populations, fatigue can lead to significant disability and have serious adverse effects on quality of life.[1,8-10] It can affect a patients self-concept, appetite, activities of daily living, family and social relationships, and decisions to continue employment or treatment,[1,5] as well as reduce a patients ability to tolerate therapy and provide self-care.
With greater appreciation of the impact of fatigue on quality of life, increased efforts to better define it and measure its effects on patients with cancer or HIV infection are ongoing. Results from recent survey initiatives have confirmed the high prevalence and significant impact of fatigue in both patient populations.[4,9,12] The findings also indicate that fatigue is a frequently overlooked and undertreated symptom partly because of perceptions that: (1) its etiology is often indeterminate, (2) it is an inevitable manifestation of the disease or treatment that must be endured, and/or (3) few interventions are available. The findings also suggest that patients and their caregivers and physicians may have inadequate dialogue and difficulty communicating about fatigue. In order to improve the quality of life of patients with cancer or HIV/AIDS, physicians should reassess their perceptions of fatigue and their approach to its diagnosis and treatment. Improved communication with patients and their caregivers can play an important role in the process, since there are recognizable causes of fatigue for which interventions can be beneficial.
The prevalence of fatigue in cancer patients who are undergoing chemotherapy ranges from 60% to almost 100%.[4,13-19] For those undergoing radiation therapy, the prevalence of fatigue usually increases over the course of treatment.[17,20,21] Results of a recent tripart survey assessing the perceptions of cancer-related fatigue in 419 cancer patients, 200 primary caregivers (usually family members), and 197 oncologists confirmed the high prevalence and adverse impact of fatigue in the cancer population. This survey was important because it was the first systematic epidemiologic assessment of a large sample of patients and those involved in their care.
Overall, 78% of patients in the tripart survey reported experiencing fatigue during the course of their disease and treatment, with 32% experiencing it on a daily basis. Oncologists reported that 76% of their patients experience fatigue, and caregivers observed fatigue in 86% of patients. Fatigue had a marked impact on patients' daily lives, with 32% rating it as having a significant impact on their daily routine and another 39% indicating that it somewhat affected their daily activities.
Numerous areas of daily life were negatively affected, including the ability to work, physical and emotional well-being, and the ability to enjoy life in the moment (Figure 1). Many patients also reported that they had to limit their social activities (57%), had trouble finishing projects (49%), and could not walk long distances (48%). Patients felt that fatigue affected their daily lives more adversely than cancer-related pain (61%), while only 37% of the oncologists believed this to be true. Fatigue also affected patients psychologically, with 12% reporting that fatigue made them want to die and approximately one-third stating that fatigue affected their concerns about mortality or survival or their hope of fighting the disease. These results are consistent with those from other studies indicating that fatigue can result in significant distress[3,18,22] and functional impairment.[11,16,17,19]
The etiology of fatigue in cancer patients is complex and most likely multifactorial. Despite considerable research, it has been difficult to identify consistent correlates of fatigue in this patient population, although pain and psychological distress are frequently implicated.[13,14,17,18,23] Factors most often associated with fatigue in cancer patients are generally classified into three categories: physiologic, psychological, and situational. Recognized common causes and correlates of fatigue for which there are specific interventions are summarized in Table 1.
Physiologic factors that may contribute to fatigue in cancer patients include anemia, chronic pain, infection, fever, surgery, and inadequate intake of nutrients secondary to anorexia, nausea, vomiting, or gastric obstruction.
One of the most common and obvious causes, anemia, may result from the cancer or its treatment regimen. Anemia contributes significantly to a decreased quality of life. Cancer-related anemia has a complex etiology and may be caused by blood loss, iron or vitamin deficiency, treatment-induced myelosuppression, hemolysis, or tumor involvement of the marrow. Chemotherapy and radiation therapy to the bone marrow, particularly the pelvis or spine, can be severely myelosuppressive. Because of increasing use of higher doses and repeated courses of chemotherapy and radiation, stem-cell depletion may be common. Iron deficiency anemia occurs most often in patients with genitourinary, gastrointestinal, and head and neck tumors, in whom chronic blood loss is common.
As a significant stressor, pain is closely linked to fatigue. It can decrease functional capacity, diminish strength and endurance, decrease appetite, and result in poor or interrupted sleep. Pain is also associated with psychological effects that contribute to fatigue, such as personal distress, depression, increased anxiety, fear, and somatic preoccupation.
The most common psychological disorders that play a role in cancer-related fatigue include depression, anxiety, anticipatory nausea and vomiting, and pain.[13,14,24] These energy-depleting states occur when a patient encounters extreme or added stress for which usual coping mechanisms are unsuccessful. Thus, it is critical that psychological complications of cancer be promptly recognized and effectively treated.[27,28] Depression in cancer patients most often results from situational stress related to the diagnosis and treatment of cancer or concomitant medications. Cancer patients at greatest risk for depression include those with advanced disease, poor physical condition, inadequately controlled pain, and preexisting mood disorders.
Sleep disturbances (eg, insomnia) and excessive inactivity/rest/immobility are the most common situational factors that contribute to fatigue in cancer patients.[16,23,24] Other situational factors include: crises, medications for concomitant illnesses or disorders, diagnostic testing, and problems with relationships. Like psychological factors, these are stressful, energy-depleting states. In a study measuring the degree of insomnia in 47 cancer patients, total sleep time per week averaged less than 50 hours in 45% of the patients and less than 40 hours in 23%, fewer hours than hospitalized medical and surgical patients. Patients reported difficulty getting to sleep and staying asleep. These results suggest that sleep disturbances may be more frequent and severe in cancer patients than in the general population. To avoid the fatigue caused by physical effort, cancer patients are often advised to rest and limit their activities. Decreased activity or bed rest induces muscular wasting and lowers functional capacity and endurance, thereby creating a self-perpetuating condition. Thus, patients gradually become accustomed to their impaired status and eventually experience it as normal.
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