The experience of fatigue is considered subjective and, not unlike pain and anxiety, remains a challenge to define. There has been a heightened awareness during the past 20 years that the incidence of fatigue is extremely high among all patients. Current research demonstrates that it is highly prevalent throughout all stages of cancer, affects both genders, and crosses all age groups (Burks, 2001; Curt, Breitbart, Cella et al., 2000; Nail, 2002). Although several authors, as well as the National Comprehensive Cancer Network (NCCN), offer definitions that highlight various aspects of the experience of extreme tiredness, there is as yet no universal or “gold standard” definition of fatigue in the context of health and disease (Glaus, 1998; NCCN, 2005; Neuenschwander & Bruera, 1998; Portenoy & Miaskowski, 1998). Fatigue remains the symptom reported most consistently by patients with a cancer diagnosis; it is considered the one symptom that is the most distressing. It interferes with daily activities of living and results in a decrease in quality of life (Glaus, Crow, & Hammond, 1994; Richardson, 1995).

With a growing interest in the treatment and study of fatigue, there is a heightened need for a common definition that would provide a better understanding of this symptom. Glaus (1998) notes that defining fatigue remains difficult in part because there are so many unanswered questions: It is not clear whether fatigue is a single entity or involves various related phenomena. What is generally agreed upon is that cancer-related fatigue is subjective and multidimensional and that it should be measured by self-assessment and self-report. It is not yet understood what causes extreme tiredness in patients with advanced illness, nor is it understood why at least 10% to 30% of patients experience fatigue that persists for months to years after the completion of treatment (Bower, Ganz, Aziz et al., 2002; Nail, 2004). The fact that there is still not an agreed-upon definition remains the greatest challenge. As early as 1987, Piper, Lindsey, and Dodd defined cancer-related fatigue as a “persistent feeling of exhaustion and decreased physical and mental capacity unrelieved by rest or sleep.” A later definition proposed by Cella, Peterman, Passik et al. (1998) defined fatigue as “a subjective state of overwhelming and sustained exhaustion and decreased capacity for physical and mental work that is not relieved by rest.” The most recent definition put forth as a result of the work of the NCCN defines fatigue as “a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning” (Mock, Atkinson, Barsevick et al., 2003; NCCN, 2005). This definition leaves out the important fact that the main difference between cancer-related fatigue and non–cancer-related fatigue is that it is unrelieved by rest (Mock, 2003). A comprehensive definition should include specific criteria such as severity, duration, and effect as well as the fact that it is not relieved by rest. It should also include the effect on quality of life and functional ability. This would increase the visibility of this problem and provide a real focus for research (Morrow, Abhay, Roscoe et al., 2005; Portenoy & Miaskowski, 1998; Winningham, Nail, Burke et al., 1994).

Fatigue may include symptoms similar to malaise, weakness, asthenia, lassitude, and loss of strength, as well as difficulty in concentrating and decreased energy (Iop, Manfredi, & Bonura, 2004). Some authors use the terms “fatigue” and “asthenia” interchangeably (Neuenschwander & Bruera, 1998). Cella and colleagues (1998) conceptualize fatigue as a multidimensional phenomenon that includes physical, emotional, and cognitive components. Ferrell, Grant, Dean et al. (1996) note that fatigue has a significant effect on all dimensions of quality of life including physical, spiritual, psychological, and social. Aaronson, Teel, Cassmeyer et al. (1999) define fatigue as the awareness of a decreased capacity for physical and/or mental activity due to an imbalance in the availability, utilization, and/or restoration of resources needed to perform activity.

Most researchers agree that cancer-related fatigue is a multicausal, multidimensional symptom (Cella et al., 1998; Glaus, 1998; Neuenschwander & Bruera, 1998; Piper, Dibble, Dodd et al., 1998; Portenoy & Miaskowski, 1998; Winningham et al., 1994). Although sparse, most reports place the incidence of fatigue in the terminally ill between 75% and 100% (Lawrence, Kupelnick, Miller et al., 2004; Maughan, James, Kerr et al., 2002; Wolfe, Grier, Klar et al., 2000). It is one of the most common symptoms reported by patients with cancer and clearly can be both extremely distressing and debilitating (Clark & Lacasse, 1998; Glaus, 1998; Portenoy & Miaskowski, 1998). High levels of fatigue may be experienced by patients receiving treatment as well as those with advanced disease. This may result in a permanent decrease in level of functioning (Given, Given, Azzouz et al., 2001; Mock, McCorkle, Ropka et al., 2002). There needs to be more research in this area. Fatigue is also a common symptom in many chronic diseases such as rheumatoid arthritis, diabetes, multiple sclerosis, and acquired immunodeficiency syndrome (AIDS), as well as the poorly understood chronic fatigue syndrome (Aaronson et al., 1999). Fatigue may precede a diagnosis of cancer and may be debilitating enough to lead patients to refuse further anticancer treatment (Neuenschwander & Bruera, 1998).

Most research into cancer-related fatigue has focused on the period surrounding treatment, and there is much work to be done to further understanding of fatigue in cancer survivors, patients with terminal disease, and adolescents. Research has just started to extend beyond the adult population (Erickson, 2003). Fatigue in cancer patients may be perceived as inevitable by care providers, family, and patients themselves (Neuenschwander & Bruera, 1998), and complaints may not be taken seriously (Clark & Lacasse, 1998). Fatigue-related problems often emerge after the more distressing symptoms such as pain or nausea have been relieved.

Fatigue is reported to affect 70% to 100% of patients regardless of age. It can be an effect of therapy or the cancer itself or both (Curt et al., 2000; Erickson, 2003; Jacobsen, Hann, Azzarello et al., 1999; Malik, Makower, & Wadler, 2001). It can be a presenting symptom as well as a symptom seen in advanced cancer and palliative care. Better management of other symptoms such as nausea, vomiting, and pain has made fatigue a more distressing symptom than it has been in the past. Fatigue as a physiological phenomenon may be a beneficial and protective symptom against overexertion during both prolonged physical and intellectual efforts (Aaronson et al., 1999). The feeling of being tired after a good exercise session or a hard day’s work can even be pleasant (Clark & Lacasse, 1998; Glaus, 1998). This phenomenon is to be distinguished from fatigue as a pathological finding that is distressing and serves no beneficial function. Mock (2003) believes that cancer patients may need to repair additional cells as a result of treatment with chemotherapy or radiation therapy. At the same time, the body has less reserve energy to perform this task as a result of anorexia, cachexia, nausea, and diarrhea. Fatigue associated with cancer has been found to be more persistent and more emotionally overwhelming and lacks the normal circadian rhythm (Glaus, 1998). It is not relieved by a good sleep and paradoxically may contribute to sleep difficulties (Engstrom, Strohl, Rose et al., 1999).

Fatigue has been associated with most severe and chronic illnesses, including cancer, end-stage organ failure, neuromuscular disorders, and major depression. However, the pathogenesis of fatigue is not yet well understood and is the subject of much speculation, conjecture, and research. Cella and associates (1998) list several factors that may contribute to cancer-related fatigue:

Most often, fatigue is the result of multiple factors, each requiring individual attention and treatment, if possible (Cella et al., 1998). Some of the potential causes listed are considered in more detail in the discussion that follows.

Researchers and clinicians agree that accurate assessment and measurement of fatigue are critical to advancing the knowledge and ability to treat effectively. There are a number of appropriate and validated tools in existence with which to assess and measure fatigue. They include the Brief Fatigue Inventory, the Revised Piper Fatigue Scale, the Cancer Fatigue Scale, the Revised Schwartz Cancer Fatigue Scale, and the Multidimensional Fatigue Inventory (Mendoza, Wang, Cleeland et al., 1999; Okuyama, Akechi, Kugaya et al., 2000; Piper et al., 1998; Schwartz & Meek, 1999; Smets, Garssen, Bonke et al., 1995). Piper and coworkers (1998) suggest that a simple rating of fatigue intensity from 0 to 10 is reasonable in many circumstances (Table 28-1). The authors add that patients should be asked the following as well:

These screening questions are helpful in determining the need for further assessment, referrals, and supportive therapies such as home care, occupational therapy, or assistive equipment (Piper et al., 1998). The symptoms of fatigue must be viewed in the context of the person’s life, level of distress, and overall treatment goals, recognizing that these goals may change over time (Portenoy & Miaskowski, 1998).

Initial assessment includes identifying temporal features, such as onset and daily patterns, determining any relationship between the fatigue and events such as chemotherapy, and assessing factors that relieve and exacerbate the fatigue. Screening laboratory tests may include complete blood cell count; electrolyte, serum calcium, creatinine, glucose, and transaminase levels; and possibly a thyrotropin (thyroid-stimulating hormone) evaluation if hypothyroidism is suspected (Walker et al., 1998).

There are several unresolved issues related to the assessment of fatigue. The first is the ability to distinguish between fatigue and depression. Fatigue and depression have common symptoms such as loss of concentration. The second issue is the use of self-reports of fatigue as a basis for clinical decision making. The third issue was the ability to detect temporal changes in fatigue. There is a lot of variability in the level of fatigue in patients receiving chemotherapy or radiation therapy. Depending on how the measurement tool is worded, it may be difficult to capture the changes over the course of the day or week (Jacobsen, 2004).

Fatigue is a multidimensional problem, and more sophisticated assessment may be helpful in some cases (Piper et al., 1998; Portenoy & Miaskowski, 1998). Although most fatigue assessment instruments have been developed for research, they may be helpful in clinical practice if they are easy to use. Multidimensional tools such as the Piper Fatigue Self-Report Scale, which looks at severity, distress, and effect of fatigue, are available for use in clinical situations and can aid in the evaluation of intervention strategies (Piper et al., 1998).

It is important to ask about fatigue during an initial history and follow-up visits with patients. As previously noted, fatigue may be viewed as inevitable by patients and families or may not be noticed until more distressing symptoms have been relieved (Neuenschwander & Bruera, 1998). It is important to ask about the five primary factors associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism (Patarca-Montero, 2004).