Purpose

Expressions like "bone tired", "exhausted", and "against the wall" are descriptions used by people with cancer to depict the overwhelming fatigue experienced (Ferrell, Grant, Dean, Funk, & Ly, 1996). Approximately 1.3 million people in the United States will be diagnosed with cancer in 2003 (American Cancer Society, 2003). Millions of other individuals are already living with the disease. Fatigue continues to be the most prevalent and disruptive symptom of cancer and its treatment regimens (Degner & Sloan, 1995; Donnelly, Walsh, & Rybicki, 1995; Mock et al., 1997; Newell, Sanson-Fischer, Girgis, & Ackland, 1999; Sarna, 1993a, 1998), often lingering beyond the treatment phase of the disease (Blesch et al., 1991). In women undergoing treatment for breast cancer, fatigue can persist for months or years following the completion of therapy (Bower, Ganz, Aziz, & Fahey, 2002). Fatigue was the most frequent and distressing cancer-related symptom occurring in women with lung cancer, two times greater than the next symptom, pain, and remains one of the most common symptoms in newly diagnosed lung cancer patients at any stage of the disease (Sarna, 1993a; Tanaka, Akechi, Okuyama, Nishiwaki & Uchitomi, 2002).

Potential causes of fatigue include preexisting conditions, physical and psychological symptoms caused by cancer, and the consequences of treatment (Winningham et al., 1994). Several underlying mechanisms have been suggested. They include biochemical changes, sleep disturbances, cognitive impairment, and nutritional status (Miaskowski & Lee, 1999; Winningham et al.). The activation of proinflammatory cytokines in response to the tumor, such as interleukin-1 beta, interleukin-6 and tumor necrosis factor, have been implicated in the development of cancer-related fatigue (Bower et al., 2002).

Since fatigue is not directly observable in most of its forms, its importance and treatment are often overlooked (Newell, Sanson-Fisher, Girgis, & Bonaventura, 1998; Tanghe, Evers, & Parodaems, 1998). Patients suffering from cancer-related fatigue may have difficulty adhering to and completing treatment regimens. Fatigue has also been identified as the main reason patients withdraw from clinical trials. The quality of life of individuals experiencing cancer-related fatigue may be less than satisfactory. The purpose of this review is to describe the state of the research evidence on fatigue in oncology patients and make recommendations for nursing practice to improve care of individuals suffering from cancer-related fatigue.

Search Strategy

Research evidence from 1998 through March, 2003 was located through searches of CANCERLIT (5 manuscripts), CINAHL (204 manuscripts), MEDLINE (6 manuscripts), and PsycINFO (2 manuscripts). Key search terms were fatigue and cancer. This systematic review references 83 individual research reports, nine psychometric studies, and two evidence-based guidelines.

What is Fatigue?

The fatigue experienced from cancer and its treatment differs greatly

The fatigue experienced from cancer and its treatment differs greatly from acute or chronic fatigue experienced by the general population...

from acute or chronic fatigue experienced by the general population from a variety of etiologies. Cancer-related fatigue is described as being a more intense, chronic, and disruptive symptom that is unrelieved by rest (Dean & Ferrell, 1995; Schwartz, 1998b). Cella, Peterman, Passik, Jacobsen, and Breitbart (1998) define fatigue as an abnormal condition that occurs on most days and persists for more than 2 weeks. Manifestations can include lack of motivation and interest in activities, exhaustion, weakness, sleep disturbances, irritability, and sadness. There appears to be a reduction in energy that is disproportionate to tasks performed, and associated distress due to decreased physical and intellectual performance related to the disease and/or treatment (Cella et al.). Adults perceive cancer-related fatigue in a multidimensional manner, including sensory, affective, behavioral, and cognitive dimensions. Sensory elements refer to the mental, physical, and emotional symptoms of fatigue. Examples of sensory elements are feeling lively/listless, strong/weak, or refreshed/tired. Affective elements denote the emotional meaning attributed to fatigue, such as pleasant/unpleasant or positive/negative sensations. Behavioral indicators include elements such as fatigue distress, and intensity and severity of fatigue. Cognitive/mood factors include the ability to concentrate and feelings such as being relaxed or tense (Piper et al., 1998).

An unsettled emotional or mental state appeared in conjunction with acute or chronic phases of fatigue. Anticipatory anxiety may have accounted for increased fatigue prevalence and intensity even before the treatment phase was well underway (Richardson & Ream, 1996; Schwartz, 1998a). High levels of fatigue were associated with poor psychosocial and interpersonal well-being (Pater, Zee, Palmer, Johnston, & Osoba, 1997) and, combined with anxiety, depression, anger, and confusion, were associated with increased levels of pain (Loge, Abrahamsen, Ekeberg, & Kaasa, 1999).

Perception of the severity of fatigue is dependent in part, on the developmental level of the individual (Woo, Dibble, Piper, Keating, & Weiss, 1998). Younger adult women (less than 60 years of age) treated for breast cancer experienced more fatigue than older women perhaps due to the more aggressive therapies given to women in this age group. These younger adult patients continued to work outside the home and care for their families while on therapies, combining to increase the level of exhaustion (Woo et al., 1998). In a study of predictors of fatigue among breast cancer survivors, age was found to be significantly negatively correlated with fatigue scores (r = -.17) (Piper, Dibble, Dodd, & Weiss, 1997).

Patients and caregivers perceive cancer-related fatigue differently (Glaus, Crow, & Hammond, 1996). Nurses underestimated the occurrence of and distress caused by fatigue (Tanghe et al., 1998). Professional caregivers perceived that patients were experiencing pain more frequently than fatigue, and judged it to be the more serious symptom of the two, while patients felt that fatigue was the symptom causing the greater difficulty (Vogelzang et al., 1997). Some patients perceived fatigue as a symptom to be endured and did not report the problem to their caregivers (Vogelzang et al., 1997) while others expressed that fatigue was not just a bothersome side effect but a major life concern (Messias, Yeager, Dibble, & Dodd, 1997). Parents of children with cancer considered it their responsibility to relieve fatigue. Health care providers saw their role as contributing to and alleviating fatigue symptoms through the care they administered.

Diagnostic criteria that would set guidelines for a clinical syndrome of cancer-related fatigue had been proposed (Cella et al., 1998). A cross-sectional study by Sadler et al. (2002) examined the prevalence of this proposed clinical syndrome of cancer-related fatigue in 51 patients who had undergone either autologous or allogeneic blood or marrow transplant. Twenty-one percent of the study sample met the criteria specified in the clinical syndrome definition. Findings suggested that using a clinical syndrome approach would be helpful in identifying patients experiencing cancer-related fatigue.

Cancer Site and Dissemination

Several studies indicated that cancer of the lung, gastrointestinal, urogenital, and hematologic systems provoked the highest levels of fatigue (Richardson & Ream, 1996; Schwartz, 1998a). Schwartz (1998a) found that patients with leukemia, non-Hodgkin’s lymphoma and testicular cancer experienced the most intense fatigue levels prior to cancer treatment as compared with individuals with breast, gastrointestinal, prostate cancer or melanoma. Schwartz also found that patients who had non-Hodgkin’s lymphoma described a fatigue that was more incapacitating than those with breast cancer, and more distressful and depressing than those with prostate cancer. In another study, fatigue was found to be more severe in patients with ovarian and lung cancer as compared to those with breast cancer. The presence of metastatic disease was associated with higher levels of fatigue than those with localized and regionalized cancers (Pater et al., 1997).

Loge et al. (1999) found that Hodgkin’s disease survivors (HDS) had higher levels of total fatigue 12 years after recovery from the disease as compared with the general population. When the controls were categorized according to health status, the HDS were more fatigued and had more frequent bouts of fatigue than the group of controls in the poorest health.

Fatigue and Cancer Treatment

Fatigue manifests

Fatigue manifests itself during cancer treatment and continues after treatment is completed.

itself during cancer treatment and continues after treatment is completed. Fatigue was the most prevalent side effect of cancer patients receiving chemotherapy (Nail, Jones, Greene, Schipper, & Jensen, 1991; Richardson & Ream, 1996; Sarna, 1998). Graydon, Bobela, Irvine, and Vincent (1995) found increasing levels of fatigue among women as chemotherapy or radiation therapy progressed. Consistent with previous studies, Schwartz (2000) found fatigue levels to rise sharply during the first 24 to 48 hours following chemotherapy for breast cancer, with older women reporting less fatigue than their younger counterparts. Younger women may have differing life stressors or a different interpretation of fatigue as compared to their older counterparts. In this study, fatigue levels were not correlated with the hematologic nadir.

Persistent fatigue during the treatment phase was associated with difficult psychological adjustment - increased depression and anxiety (Longman, Braden, & Mishel, 1999b). In some cases, the mode of administration and particular chemotherapeutic regimens produced greater fatigue. Fatigue was greatest in those patients who received therapies that included the administration of a bolus infusion in addition to continuous chemotherapy infusions as compared with weekly bolus injection alone. Combinations of certain drug regimes such as Cisplatin, and 5-Fluorouracil induced higher fatigue levels as compared with weekly 5-Fluorouracil and Levamisole (Richardson & Ream, 1996).

Intensity of fatigue worsens with the cumulative effects of cancer treatment. Greater fatigue was related to more sleep problems, mouth sores,

Intensity of fatigue worsens with the cumulative effects of cancer treatment.

and nausea (Jacobsen et al., 1999). Greater fatigue was also related to lower activity levels among women on chemotherapy for breast cancer (Berger, 1998). Fatigue has been shown to increase at intervals over the course of cancer treatment. Irvine and colleagues (1998) found that women undergoing adjuvant chemotherapy for breast cancer experienced heightened fatigue at or before the midpoint between chemotherapy cycles; however, fatigue did not appear to increase with subsequent infusions. In this study, women reported an increased level of fatigue even prior to the initiation of treatment when compared to healthy controls. It has been hypothesized that anticipatory anxiety or residual physical and psychological stress associated with breast cancer surgery may have accounted for this finding (Irvine, Vincent, Graydon, & Bubela; Jacobsen et al.).

Biotherapy agents such as interferon and interleukin-2 have been known to cause both mental and physical fatigue when administered for the treatment of cancer. Severe fatigue has been reported to be a dose-limiting toxicity of these drugs, often accompanied by emotional changes and/or cognitive deficits (Winningham et al., 1994).

Fatigue in patients receiving radiation therapy increased significantly during the first two weeks of treatment, reaching a plateau from 14 days to the last week of treatment, returning to pretreatment levels several weeks after treatment ends (Irvine, Vincent, Graydon, & Bubela, 19980; Smets et al., 1998; Visser & Smets, 1998). A study by Jacobsen and colleagues (1999) found that patients receiving radiation therapy for breast cancer, prostate cancer, lymphoma, and ovarian carcinoma experienced increased fatigue over the course of radiation therapy, but fatigue returned to pre-treatment levels at 3 to 6 months post-treatment. Smets et al. found that people who had been treated with radiation therapy and were subsequently disease-free nine months later were no more fatigued than the general population. However, 34 percent of the patients found post-treatment fatigue levels to be worse than anticipated, and 39 percent felt fatigue was one of the most distressing symptoms.

Radiation therapy can have negative effects on muscle function. In a study by Monga et al. (1997) of 13 men undergoing radiation treatment for prostate cancer, the neuromuscular efficiency of the anterior lateral muscle of the leg (tibialis anterior) declined during treatment. No abnormalities in fatigue levels were found in cardiopulmonary or psychologically-related fatigue measures at any time during the investigation. It is hypothesized that radiation to the pelvic area for the treatment of prostate cancer accelerates fatigue (decreased neuromuscular efficiency following sustained contraction) in fast-twitch muscles such as the tibialis anterior muscle. In most patients, this was reversed 5 to 6 weeks after radiation treatments ended, indicating alterations in muscle function as a result of radiation are not long-term. Conversely, Walker, Nail, Larsen, Magill, and Schwartz (1996) found in a sample of 9 men with prostate cancer and 11 women with breast cancer undergoing radiation therapy that fatigue was the most common long-term side effect, lasting up to 20 months. In another instance, palliative radiation therapy administered to patients with advanced, non-small cell lung cancer was found to relieve localized tumor-related symptoms such as cough, dyspnea and hemoptysis; however, fatigue either remained unaffected or worsened (Lutz et al., 1997). A study conducted by Stone, Richars, A’Hern, and Hardy (2001) found no significant increases in fatigue scores among 35 men with prostate cancer and 34 women with breast cancer (X age = 63 years; range 42-79) undergoing radiotherapy. However, the most important predictor of fatigue levels after radiotherapy was the baseline fatigue level prior to the start of treatment. Baseline fatigue scores were also found to be significantly related to baseline global quality of life and physical functioning.

Studies have been done comparing patients receiving chemotherapy, radiation therapy, surgery, bone marrow transplantation, or combination therapy. Fatigue levels were worst for those on combination therapies and under active treatment (Schwartz, 1998a). Fatigue levels were higher for those on combination chemotherapy regimens with a trend toward increased fatigue in patients with an advanced stage of disease (Richardson & Ream, 1996). In one study, all 46 women treated for breast cancer with breast-conserving surgery scheduled to receive radiation reported fatigue at the beginning of their treatment program (Mock et al., 1997). Fatigue levels increased significantly when chemotherapy followed surgery (Wyatt & Friedman, 1998). Although these findings suggest that early-onset fatigue may be due to the previous surgery rather than the adjuvant therapy (Hickok, Morrow, McDonald, & Bellg, 1996), Berger and Farr (1999) found no relationship between the length of time since surgery and the fatigue levels.

Molassiotis (1999) found that patients who had undergone bone marrow transplant were more tired, anxious, and depressed than those receiving maintenance chemotherapy. In a study of breast cancer survivors at least 18 months beyond their treatment regimen, Woo et al. (1998) found the highest levels of fatigue in women who had received a combination of chemotherapy and radiation as compared with women receiving chemotherapy alone. Women treated with radiation therapy alone had the lowest levels of fatigue.

There are several ways to measure fatigue. The Piper Fatigue Scale (original and revised versions) (Piper et al, 1998), the Schwartz Cancer Fatigue Scale (Schwartz, 1998b), the Multidimensional Fatigue Symptom Inventory (Stein, Martin, Hann, & Jacobsen, 1998), the Multidimensional Fatigue Inventory (Smets, Garssen, Bonke, & de Haes, 1995), and the Multidimensional Assessment of Fatigue Scale (Winstead-Fry, 1998) are self-report scales which measure the multi-dimensionality of fatigue as related to cancer. Self-care diaries written by clients (Nail et al., 1991) proved to be a useful tool for nurses in identifying side effects and self-care activities (Broeckel, Jacobsen, Horton, Balducci, & Lyman, 1998)

Associated Factors

Since cancer and its treatments affect the entire person, fatigue is often associated with psychological and physical factors (Irvine et al., 1998; Sarna, 1993a; Smets et al., 1998). Pretreatment psychological distress can increase fatigue. During treatment, symptom distress may rise causing a disruption in activities (Irvine et al., 1998). This change in stamina may increase difficulties of ambulation, problems accomplishing household chores, and modifications in recreational activities (Sarna, 1993b).

High levels of fatigue decrease quality of life, functional status, and symptom management (Burrows, Dibble, & Miaskowski, 1998; Courneya & Friedenreich, 1997; Lovely, Miaskowski, & Dodd, 1999). Fatigue from cancer engenders hopelessness and uncertainty affecting a person’s spiritual quality of life (Ferrell, Grant, Dean, Funk, & Ly, 1996; Ferrell, Grant, Funk, Otis-Green, & Garcia, 1998).

Fatigue that is detrimental to the quality of life, and leads to a loss of employment, has drastic psychosocial consequences for the individual (Pearce & Richardson, 1996).

The fear of cancer recurrence affects psychological adjustment, increasing fatigue.

Burden from the side effects of treatment leads to poor psychological adjustment that worsens as fatigue persists (Longman et al., 1999b). The result is a decreased ability to perform self-care activities (Longman, Braden, & Mishel, 1999a; Sarna, 1993b). A decrease in self-care activities such as exercise further diminishes one’s satisfaction with life (Courneya & Friedenreich, 1997). The fear of cancer recurrence affects psychological adjustment, increasing fatigue. When caregivers minimize a patient’s fatigue, this may increase their psychological stress (Ferrell et al.,1996; Ferrell et al., 1998).

Many researchers have found greater anxiety and depression to be related to greater cancer-related fatigue (Akechi, Kugaya, Okamura, Yamawaki, & Uchitomi, 1999; Hann et al., 1998; Mock et al., 1997; Piper et al., 1997). However, Visser and Smets (1998) found that depression remained stable after treatment but level of fatigue declined in a sample of 250 men and women treated for cure or control of a variety of cancers. Treatment and post treatment fatigue experienced by women treated for breast cancer with radiotherapy, chemotherapy, or bone marrow transplant was found to be more intense, longer lasting and caused more interference with functioning as compared to healthy controls (Hann et al., 1998).

It has been suggested that altered or disrupted circadian rhythms may be implicated in cancer-related fatigue. There is evidence from experimental tumor models to suggest that cancer and chemotherapy may alter circadian rhythms. The disruption of circadian rhythm has been significantly correlated with increases in fatigue and depression and quality of life in patients receiving chemotherapy for breast cancer. These disruptions in circadian rhythms were noted early in chemotherapy treatment cycles and may help predict patients at risk for the development of fatigue or mood disturbance during chemotherapy (Mormont & Waterhouse, 2002; Roscoe et al., 2002).

Fatigue and Pain

Studies of cancer patients frequently reported a link between fatigue and pain (Burrows et al., 1998; Ferrell et al., 1996; Glover, Dibble, Dodd, & Miaskowski, 1995; Hickok et al., 1996; Miaskowski & Lee, 1999; Sarna, 1993a; Winningham et al., 1994; Wyatt & Friedman, 1998). Pain, fatigue, mood state, and quality of life were intertwined. Long lasting pain and associated fatigue affected the quality of life in physical, psychological, social and spiritual domains of an individual's life (Ferrell et al., 1996).

High levels of pain intensity and duration, interfering with mood and ability to function (Ferrell et al., 1996; Vogelzang et al., 1997), were related to higher levels of fatigue (Blesch et al., 1991; Glover et al., 1995). During radiation therapy the fatigue experienced by patients increased in a linear fashion over the treatment course, while the percentage of patients who experienced pain remained at a constant level (Hickok et al., 1996).

In a descriptive, correlational study of 24 outpatients receiving radiation therapy for bone metastases, Miaskowski and Lee (1999) found that cancer patients suffering from intense pain also had increased levels of fatigue. Pain disturbs sleep leading to increased fatigue. The use of tranquilizers was a part of relief-seeking for pain and fatigue (Miaskowski & Lee).

Fatigue and Digestive Problems

Anorexia, nausea and vomiting can be common symptoms during cancer treatment (Hjermstad, Evensen, Kvaloy, Fayers, & Kaasa, 1999; Newell et al., 1999). Some patients reported frequent occurrence of mouth sores, nausea, and vomiting which was associated with worsening fatigue after the start of chemotherapy (Jacobsen et al., 1999). Patients whose nausea was better controlled showed significantly less rise in fatigue when on chemotherapy treatments (Pater et al., 1997).

Fatigue and Sleep Disturbance

Fatigued cancer patients often reported sleep disturbances such as insomnia (Sarna, 1993a; Mock et al., 1994). Patients reporting poorer sleep quality and sleeping during the day had more severe fatigue (Broeckel et al., 1998). Berger and Farr (1999) found that patients with higher cancer-related fatigue levels were generally less able to adjust to demands of increased activity and quiet sleep at night. An increased number of night awakenings, less daytime activity, and more daytime naps increased the levels of fatigue.

Contradictory findings were reported by Miaskowski and Lee (1999). Using wrist actigraphy to measure sleep time, efficiency, and number of awakenings, they found that the percentage of time spent napping during the day was not related to fatigue severity, sleep efficiency, or number of nighttime awakenings. Those who slept more during the night also slept more during the following day. They concluded that pain, not fatigue, was the main cause of night awakenings.

Fatigue and Menopause

Menopausal symptoms were significantly linked to fatigue severity.

Menopausal symptoms were significantly linked to fatigue severity. Perimenopausal women reported higher fatigue levels than premenopausal women (Piper et al., 1997). Women who underwent surgery and chemotherapy for breast cancer and who reported more psychological, somatic, and psychosomatic menopausal symptoms had fatigue of greater severity (Broeckel et al., 1998). This severity may be related to intensified depressive symptoms or nighttime sleep disturbances due to night sweats.

Fatigue and Anemia

Anemia resulting from cancer treatment can be a contributing factor in cancer-related fatigue. Many traditional chemotherapy regimens are associated with significant anemia, which can have a negative impact on quality of life. The relationship between fatigue and hemoglobin levels can vary greatly among people with cancer. A rapid drop in the hemoglobin level is more likely to precipitate symptoms of anemia such as fatigue, as compared with a slower decline in the hemoglobin level. In a longitudinal study of 17 adults receiving chemotherapy for early-stage breast or ovarian cancer, Payne (2003) found that subjective fatigue was experienced by the majority subjects. Over time, the pattern of fatigue was irregular. Fatigue levels intensified at three months and continued following the end of treatment. The trajectory of fatigue from baseline to three months demonstrated significant physiologic changes over time in hemoglobin in the breast cancer patients (p = 0.02). Changes were also observed in nighttime melatonin levels (p = 0.03) in breast and ovarian patients. While differences in daytime melatonin levels were not significant, the levels did change from baseline to six months.

Treatment of cancer treatment-induced fatigue can consist of transfusion therapy and/or the administration of Epoetin alpha (recombinant human erythropoietin) (Turner et al., 2001). Poor performance status was related to high levels of fatigue (Pater et al., 1997). Glaspy and colleagues (1997) treated over 2000 fatigued, anemic cancer patients with epoetin alfa. These patients reported increased energy levels that were positively related to quality of life, even in patients in advanced stages of cancer.

Fatigue and Non-Cancer Comorbidities

Comorbid illnesses that are not related to a diagnosis of cancer can contribute to symptoms of fatigue in the individual with cancer. Comorbidities such as infection, cardiac, pulmonary, hepatic, renal, neurologic, and endocrine dysfunction require review and assessment as to their potential contribution to fatigue experienced. Optimum treatment of underlying comorbid illness may assist in lessening fatigue levels (National Comprehensive Cancer Network Clinical Practice Guidelines, 2003) (www.nccn.org).

Strategies for Treating Fatigue

Cancer patients cope with their fatigue as unique individuals (Glaus et al., 1996; Pearce & Richardson, 1996), attempting various strategies and engaging in a variety of activities in hopes of being less fatigued or gaining strength (Fieler, Nail, Greene, & Jones, 1995). Coping strategies used by fatigued cancer patients included acceptance of what one cannot change, trying to think positively, humor, trying to maintain normalcy, denial, catastrophizing, energy conservation and trust in those providing social support (Broekel et al., 1998; Fieler et al., 1995; Johnson & Kelly, 1990; Pearce & Richardson; Walker et al., 1996). Those former chemotherapy patients who used catastrophizing as a coping mechanism experienced significantly more severe fatigue (Broekel et al.). Denial was not beneficial while a supportive social network provided strength for the physical and emotional aspects of fatigue (Pearce & Richardson). Obtaining information about treatment and prognosis helped patients with self-evaluation of normalcy (Walker et al., 1996).

Educational Strategies

Patients expressed a need for more information about the causes and effects of cancer-related fatigue but had difficulty finding answers (Ashbury, Findlay, Reynolds, & McKerracher, 1998).

Education concerning the expected pattern and duration of cancer-related fatigue should be provided to all patients.

Accessibility of patient-centered information proved to be problematic. Educational resources that were available failed to address major issues confronting patients or were written at too high a reading level for most readers (Sarna & Ganley, 1995). Early work by Johnson, Nail, Lauver, King, and Keys (1988) found enhanced quality of life and functioning when patients are provided with preparatory information regarding fatigue and other treatment-related symptoms. Education concerning the expected pattern and duration of cancer-related fatigue should be provided to all patients. In addition, the National Comprehensive Cancer Network Clinical Practice Guidelines (2003) suggest that patients be counseled regarding strategies that may be helpful in coping with fatigue.

Self-Care Strategies

Self-care activities have focused on energy conservation (Fieler et al., 1995; Foltz, Gaines, & Gullatte, 1996; Graydon et al., 1995; Nail et al., 1991), symptom management (Foltz et al., 1996; Larson, Dodd, & Aksamit, 1998; Miaskowski & Lee, 1999), information seeking (Ashbury et al., 1998; Sarna & Ganley, 1995), and attention restoration (Cimprich, 1993).

Much of the research conducted on cancer-related fatigue has been based on the work of energetics, which sees energy as a balance between consumption and expenditure (Foltz et al., 1996; Graydon et al., 1995; Nail et al., 1991). Fatigue is seen as a deficit, with physiological and psychosocial dimensions requiring adaptive responses (Winningham et al., 1994).

Energy Conservation

Energy conservation refers to the restriction of energy-requiring activities to prevent energy depletion, such as setting priorities and pacing of activities (Barsevick, Whitmer, Sweeney & Nail, 2002). The most commonly employed energy conservation strategy for some patients was to increase their sleep time by taking extra naps, going to bed earlier, or sleeping later (Graydon et al., 1995; Nail et al., 1991). Fieler and colleagues (1995) found that patients tried a variety of measures to ameliorate fatigue. Among the most frequent were taking extra naps and rest periods, eating well, and thinking positively. Least used activities included staying away from children and increasing exercise. While the data clearly indicated that patients used behaviors to reduce the side effects of chemotherapy, the efficacy of these measures could not be concluded from this study. Barsevick and colleagues conducted a single-group pilot study designed to examine the feasibility of a 3-session telephone energy conservation and activity management (ECAM) intervention with 14 individuals undergoing treatment for breast, lung, and colorectal cancer, with a minimum of 3 cycles of chemotherapy or 6 weeks of radiation therapy. The telephone ECAM intervention was administered during times when fatigue would be expected from treatment. For those receiving chemotherapy, the intervention was administered during the first 3 weeks of treatment and at weeks 3, 4, and 5 for individuals receiving radiation. Session one included information regarding the nature of cancer-related fatigue and energy-conservation skills for managing it. Participants kept a daily journal to monitor fatigue, rest, activity and other symptoms. In the second session, participants were asked to develop a plan for maintaining valued activities while minimizing interference from fatigue. The last session focused on evaluation and revision of the plan. The overall fatigue patterns for both groups were lower than the non-equivalent control group. The intervention appeared to be well tolerated and acceptable to patients.

Davidson, Waisberg, Brundage, and Maclean (2001) tested a 6-session group sleep therapy program consisting of stimulus control and relaxation therapy in 12 patients (11 women, 1 man) previously treated for breast, gastrointestinal, lung, or gynecologic cancer who reported insomnia. Data was collected using a sleep diary, the Sleep Impairment Index, the Hospital Anxiety and Depression Scale, and 3 subscales (fatigue, pain, insomnia) from the European Organization for Research and Treatment of Cancer QLQ-C30. Participants reported improved sleep quality and fatigue levels. A similar study by Berger, Von Essen, & Kuhn et al. (2002), tested the feasibility of an individualized sleep promotion plan (ISPP) in 25 women undergoing 4 cycles of adjuvant doxorubicin-based chemotherapy for Stage I-II breast cancer. Each woman was asked to develop an ISPP containing 4 components: sleep hygiene, relaxation therapy, stimulus control, and sleep restriction techniques. Data were collected from a daily diary kept by the women, the Pittsburgh Sleep Quality Index, a wrist actigraph, and the Piper Fatigue Scale administered 2 days prior and 7 days after each cycle of chemotherapy. Although adherence rates to the intervention varied, fatigue remained stable 2 days after each treatment; and the mean fatigue intensity experienced daily was lower at cycle 3, but rebounded at cycle 4. A similar study conducted by Quesnel, Savard, Simard, Ivers, and Morin (2003) found that using this type of cognitive-behavioral therapy showed benefits in improving insomnia in patients with breast cancer. While further research in this area is needed, encouraging behaviors that promote restful sleep may assist in managing fatigue during chemotherapy. Other self-care actions that best assisted in the management of fatigue were increasing time in bed, sleeping later, going to bed earlier, or napping (Foltz et al., 1996). Other strategies such as getting fresh air, exercising, keeping busy, and drinking caffeine demonstrated variable effectiveness.

Self-Management of Related Symptoms

The management of symptoms other than but related to fatigue in cancer patients is also connected to the correction of an energy deficit (Winningham et al., 1994). Studies conducted on symptom distress found that fatigued patients took medications for sleep disturbances, nausea, and pain (Foltz et al., 1996; Graydon et al., 1995; Miaskowski & Lee, 1999). Some patients sought pain relief through the use of tranquilizers (Tanghe et al., 1998). For those experiencing nausea, 50 percent used rest as a means of nausea control, and 80 percent reported taking antiemetics (Foltz et al., 1996). Patients taught to understand, track and manage their symptoms experienced a greater sense of control, as active participants in their own care.

Attention Restoration

Attentional fatigue, considered part of the sensory dimension of the fatigue experience, is defined as a decrease in the capacity to concentrate or direct attention (Cimprich, 1993). Cimprich found that women with breast cancer had manifestations of this form of fatigue 3 months following surgery. She found that participants who planned and carried out attention-restoring activities for 20 to 30 minutes at least three times a week had consistently higher attentional scores than those who did not. Restorative activities included walking or sitting in a park, bird watching, and tending to flowers or plants. These therapeutic moments were inexpensive, ordinary activities, and resulted in gains in attentional capacity and decreased attentional fatigue over time. Consistent with these findings are the results obtained by Schneider, Prince-Paul, Allen, Silverman, and Talaba (2003) when using a virtual reality distraction intervention to mitigate chemotherapy-related symptom distress. A sample of 20 women with breast cancer aged 18-55 were randomly assigned to receive the virtual reality distraction intervention during one chemotherapy treatment and received no distraction intervention (control condition) during an alternate chemotherapy treatment. Analysis demonstrated a significant decrease in the Piper Fatigue Scale (p = .04) scores immediately following chemotherapy treatments when participants used virtual reality. The intervention involved wearing an eight-ounce head-mounted display, which portrayed encompassing images, such as deep sea diving and going through an area museum. Further studies in this area that examine attentional interventions in diverse cancer populations are needed.

Exercise Strategies

Counter to the idea that fatigued patients should limit activities and conserve energy is the theory that decreasing activity because of a cancer diagnosis and subsequent treatment may increase the rate of decline and hinder healing (Schwartz, 1998a). In fact it has been found that daytime inactivity increased cancer-related fatigue levels (Berger & Farr, 1999). Early work by MacVicar, Winningham, and Nickel (1989) demonstrated the benefits of cycling exercise on physical functioning and feelings of control in women undergoing treatment for breast cancer. Graydon et al. (1995) studied patients that used energy conservation strategies during cancer treatment and found that reduced physical activity contributed to increased levels of fatigue and further debilitation. The most effective strategy for fatigue relief was sleeping; but exercise, "doing something different," and interacting with friends also proved to be very helpful ways of relieving fatigue.

Athletes who had cancer, studied by Schwartz (1998a), exercised

Exercise interventions can assist in retarding debilitating weakness, fatigue, and functional decline in those with disease-associated inactivity.

with a resulting decrease in the intensity, frequency, and duration of fatigue. They described feeling renewed and more alert. Exercise interventions can assist in retarding debilitating weakness, fatigue, and functional decline in those with disease-associated inactivity. Using a one-group, pre-test-posttest design, Schwartz (2000) found that women with Stage II and III breast cancer who engaged in an 8- week, home-based, 15-30 minute aerobic exercise program 4 days a week had fewer days of severe fatigue and a pattern of decreasing levels of fatigue with each cycle of chemotherapy as compared to non-exercisers. Cancer patient exercisers reported a significantly improved quality of life compared to non-exercisers (Young-McCaughan & Sexton, 1991). MacVicar and colleagues (1989) tested an interval-training cycle-riding regimen with women receiving chemotherapy for breast cancer. The women realized a 40 percent improvement in energy levels and were able to ride longer and harder at posttest than at pretest.

Mock and colleagues (1994) found similar outcomes through a structured exercise program of walking for 14 women with Stage I or II breast cancer receiving adjuvant treatment. The group of women that walked routinely, with structured guidance, adapted better to physical symptoms of chemotherapy, physical functioning and psychosocial changes. They experienced consistent and progressive improvement during the course of chemotherapy, while the women who did not exercise got progressively weaker. In a more recent study Mock et al. (2001) found improved quality of life and physical functioning, and significantly less fatigue and emotional distress in 52 women with Stage I, II or IIIa breast cancer receiving adjuvant chemotherapy or radiation who exercised at least 90 minutes 3 days a week as compared to less active women.

A self-paced walking exercise program was found to be effective for women with early stage breast cancer who received breast-conserving surgery and were scheduled to receive radiation therapy (Mock et al., 1997). Women in the treatment group started walking at the beginning of radiation therapy and gradually increased the distance walked as the treatment progressed. These women had better physical functioning by the end of the treatment regimen. As the distance increased, fatigue and sleeping difficulties decreased. The usual care group experienced consistent levels of fatigue throughout the treatment period.

Dimeo, Rumberber, and Keul (1998) measured muscle metabolism, heart rate and stress levels in five patients with varying cancers during a monitored exercise program. All five people experienced decreased fatigue and improved physical functioning over the six weeks of daily treadmill walking and were able to return to normal daily functioning without any significant limitations.

Quality of life in 130 patients with colorectal cancer also was related to exercise patterns in a retrospective study by Courneya and Friedenrich (1997). Individuals who maintained exercise regimens during diagnosis and treatment or returned to an exercise routine after treatment reported better quality of life than those cancer survivors who were inactive after treatment even though they had exercised regularly before the diagnosis. This is because some quality of life issues (weight gain, muscle atrophy, fatigue) related to cancer treatment have a physical basis and exercise may begin to address some quality of life issues for people recovering from cancer. It should be noted that the majority of exercise-based studies have consisted of a structured exercise program for women with breast cancer. Additional research is needed that would include different exercise regimens and other cancer diagnostic groups.

Anemia Control

Anemia can contribute to fatigue and reduced quality of life in individuals with cancer (Cella & Bron, 1999). Results of many randomized clinical trials support the treatment of cancer-related anemia. In a review article, Turner et al (2001) reported the effects of erythropoietin alpha on quality of life quality of life in patients with cancer-related anemia in 5 randomized, controlled trials (RCTs) and 2 large, open-labeled non-randomized community-based studies. Nineteen RCTs and 21 comparison trials were also examined for the effects of erythropoietin alpha on blood transfusion requirements. Analysis supported the use of erythropoietin alpha in terms of improved and a reduction in the need for transfusions.

Evidence-based recommendations for clinical practice are summarized below. Table 1 contains recommendations for symptom assessment. Table 2 provides considerations for choosing tools to measure aspects of cancer-related fatigue. Table 3 summarizes strategies for managing fatigue.

 

Table 1. Symptom Assessment

Perform a detailed, multidimensional assessment to find precipitating, exacerbating and relieving factors related to symptom distress (Blesch et al., 1991; Ferrell et al., 1998; Hoskins, 1997; Johnson & Kelly, 1990; Leddy, 1997; Sarna, 1998; Sarna & Brecht, 1997). Assess patients throughout their treatment regimens for changing levels of fatigue, its effects on quality of life, and the need for interventions, including palliative care services (Berger, 1998; Donnelly et al., 1995; Johnson & Kelly, 1990; Molassiotis, 1999; Richardson & Ream, 1996; Sarna, 1993a, 1998; Tanghe et al., 1998). Evaluate the patient for symptoms of depression and anxiety before and during treatment regimens, and monitor levels of depression and anxiety throughout the treatment period (Akechi et al., 1999; Hockenberry-Eaton et al., 1998; Jacobsen et al., 1999; Newell et al., 1999; Piper et al., 1997). Measure pain’s effect on fatigue and quality of life. Implement pain management strategies that decrease fatigue levels (Burrows et al., 1998; Glover et al., 1995; Hickok et al., 1996; Jacobsen et al., 1999; Miaskowski & Lee, 1999). Appraise patients’ sleep patterns and implement strategies to deal with sleep disturbances (Berger & Farr, 1999; Broeckel et al., 1998; Miaskowski & Lee, 1999; Piper et al., 1997; Sarna, 1993a). Intervene to control nausea’s effect on fatigue (Newell et al., 1999; Pater et al., 1997). Work with the patient and family caregivers to improve assessment and find ways to minimize fatigue (Hockenberry-Eaton et al., 1998; Messias et al., 1997; Ng & von Gunten, 1998; Pearce & Richardson, 1996; Richardson & Ream, 1996). Identify women with cancer at risk for increased fatigue in relation to their menopausal status (Piper et al., 1997), and consider non-hormonal treatments of vasomotor symptoms (i.e. night sweats) associated with menopause in post chemotherapy women (Broeckel et al., 1998). Evaluate patients’ hemoglobin-related energy levels for the need to administer blood transfusions and/or epoetin alfa for the treatment of fatigue related to anemia (Glaspy et al., 1997; Monti, Castellani, Berlusconi, & Cunietti, 1996; Turner et al., 2001).

 

Table 2. Instruments of Assessment

Use tools that measure the aspects of cancer-related fatigue that are most appropriate considering the following: Fatigue’s multidimensionality (Pater et al., 1997; Piper et al., 1998; Schneider, 1998; Schwartz, 1998b; Schwartz & Meek, 1999; Smets et al., 1995; Stein et al., 1998; Taplin, Blanke, & Baughman, 1997) Frequency and intensity of fatigue (Lutz et al., 1997; Mendoza et al., 1999; Schneider, 1998; Winstead-Fry, 1998) Self-care behaviors (Fieler et al., 1995; Foltz et al., 1996) Sleep (Miaskowski & Lee, 1999) Use fatigue inventory tools as a means to improve communication between patients and caregivers (Mendoza et al., 1999).

 

Table 3. Strategies

Energy conservation strategies Employ sleep promoting, cognitive-behavioral strategies if insomnia is present (Berger, Von Essen et al., 2002; Quesnel et al., 2003). Exercise strategies Activate a monitored exercise program to reduce fatigue as appropriate (Berger & Farr, 1999; Dimeo et al., 1998; Graydon et al., 1995; Johnson & Kelly, 1990; MacVicar et al., 1989; Mock et al., 1994, 1997; Schwartz, 1998a; Young-McCaughan & Sexton, 1991). Coping Strategies Keep communications open so that patients can express the presence and effect of fatigue (Hoskins, 1997; Irvine et al., 1998; Loge et al., 1999; Messias et al., 1997; Monga et al., 1997; Pearce & Richardson, 1996; Vogelzang et al., 1997). Communicate to patients before treatment that fatigue is "normal", usually transitory, and not necessarily a symptom of treatment failure (Hoskins, 1997; Irvine, Vincent, Graydon, & Bubela, 1998; Loge, Abrahamsen, Ekeberg, & Kaasa, 1999; Messias, Yeager, Dibble, & Dodd, 1997; Monga et al., 1997; Pearce & Richardson, 1996; Vogelzang et al., 1997). Provide patients with information about the likelihood of cancer-related fatigue and available therapies (Ashbury et al., 1998; Hoskins, 1997; Jacobsen et al., 1999; Lovely et al., 1999; Monga et al., 1997; Nail et al., 1991; Richardson & Ream, 1996; Walker et al., 1996; Woo et al., 1998). Employ attention restoring activities such walking in the park, or pleasant distractions (Cimprich, 1993; Schneider, 2003; Schneider et al., in press). Self-Care Strategies Teach range of motion exercises before breast surgery, to strengthen muscles and improve mood state (Wyatt & Freidman, 1998). Educate patients on the proper use of pain medication and tranquilizers (Miaskowski & Lee, 1999). Encourage cancer patients to engage in modest recreational activities 20 to 30 minutes a day, about three times a week to prevent attentional fatigue (Cimprich, 1993). Promote group activities to increase social support and personal growth (Johnson & Kelly, 1990; Young-McCaughan & Sexton, 1991). Information Seeking Strategies Create information packets and teaching materials that address the specific needs of people living with cancer-related fatigue (Magnusson, Karlsson, Palmblad, & Leitner, Paulson, 1997); write them at an appropriate reading level (Sarna & Ganley, 1995). Supply written instructions, advice, and information to patients, because of cancer-related cognitive impairment related to fatigue (Cimprich, 1993; Woo et al., 1998). Schedule the patient appointments with consistent health care professionals whenever possible, to improve correctness of perceptions, detection of problems, and treatment compliance (Newell et al., 1998).

Author

Constance Visovsky PhD, RN, ACNPN
e-mail: cxv6@cwru.edu

Constance Visovsky PhD, RN, ACNP received her Bachelor’s and Master’s degrees in Nursing from the University of Rochester in Rochester, NY. She received her PhD from Case Western Reserve University in Cleveland, OH. Her program of research is focused on the neurotoxic and myotoxic effects of chemotherapy and biotherapy on individuals undergoing cancer treatment. She has an interest in resistance exercise as a means of ameliorating these effects. She is currently an Assistant Professor and NCI-Translational Oncology Research Post-Doctoral Fellow at Case Western Reserve University. In addition, Dr. Visovsky also maintains an active practice as an acute care nurse practitioner at University Hospital Health Systems of Cleveland’s Ireland Cancer Center.

Susan M. Schneider PhD, RN, CS, AOCN
e-mail: schne021@mc.duke.edu

Susan M. Schneider PhD, RN, CS, AOCN is an Assistant Professor and Director of the Graduate Oncology Nursing Program at Duke University School of Nursing. She received her Doctorate in nursing from Case Western Reserve University in Cleveland, OH; her Master’s in Science degree from Texas Women’s University, and her Bachelor of Science in Nursing from the University of Akron in Akron, OH. Dr. Schneider has extensive experience in pediatric and adult oncology nursing. She holds certification as a Clinical Nurse Specialist and as an advanced oncology-certified nurse. Her research interests include the management of symptom distress in cancer patients and the use of distraction interventions to enhance coping. She has received research funding from the Oncology Nursing Foundation, Case Western Reserve University’s Comprehensive Cancer Center, and the National Institute for Nursing Research.

The Sarah Cole Hirsh Institute for Best Nursing Practices of the Case Western Reserve University Frances Payne Bolton School of Nursing, Cleveland, Ohio, USA
http://fpb.cwru.edu/HirshInstitute

The Hirsh Institute's mission is to build a repository of best nursing practices based on research findings. Institute activities include: disseminating the most current scientific evidence on best nursing practices to clinicians, educators, administrators, and policy makers; guiding nursing research by identifying areas where scientific evidence is lacking; and conducting certificate programs for nursing staff to identify and implement evidence based practice.

Young-McCaughan, S. & Sexton, D.L. (1991). A retrospective investigation of the relationship between aerobic exercise and quality of life in women with breast cancer. Oncology Nursing Forum, 18, 751-757.

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