Cancer Therapies
Anemia
Nutrition Factors
Psychologic Factors
Cognitive Factors
Sleep Disorders and Inactivity
Medications

Although fatigue is clearly prevalent in patients with cancer, it has been difficult to identify consistent correlates of fatigue in this patient population. The factors most often implicated have been the following:[1-8]

• Cancer treatment.
• Anemia.
• Medications.
• Cachexia/anorexia.
• Metabolic disturbances.
• Hormone deficiency.
• Psychological distress.
• Sleep disturbances.
• Excessive inactivity.
• Pulmonary impairment.
• Neuromuscular dysfunction.
• Pain.
• Infection.
• Concomitant medical illness.

Fatigue is a common symptom that accompanies surgery, chemotherapy, radiation therapy, and biologic response modifier therapy. Chemotherapy-related and radiation therapy–related fatigue may be associated with anemia or with an accumulation of cell destruction end products.[9] In the case of radiation therapy, fatigue may be caused by increased energy requirements to repair damaged epithelial tissue.[10]

A number of pathologic, environmental, psychologic, and nutritional factors have been associated with chemotherapy-related fatigue. Some psychologic responses to the diagnosis and treatment of cancer are mood variations and sleep-pattern disruptions. Physiologic responses including nausea, vomiting, chronic pain, and cachexia have also been cited as factors causing fatigue.[11]

Fatigue has long been associated with radiation exposure. The phenomenon of fatigue accompanying radiation therapy, however, is not well understood.[11] A number of research studies document the existence of a fatigue syndrome that is not specific to the disease type or to the radiation site, and that demonstrates a gradual decline in fatigue in the patient after treatment is completed.[10,12-15] Some of these studies suggest, however, that not all patients return to pretreatment energy levels. Specific etiologic factors and correlates of fatigue associated with radiation therapy have not been identified.[11] Risk factors for persistent low energy in cancer patients include older age, advanced disease, and combination-modality therapy.[16]

Fatigue is a dose-limiting toxicity of treatment with a variety of biotherapeutic agents. Biotherapy exposes patients with cancer to exogenous and endogenous cytokines.[17] Biotherapy-related fatigue usually occurs as part of a constellation of symptoms called flulike syndrome. This syndrome includes fatigue, fever, chills, myalgias, headache, and malaise.[18] Mental fatigue and cognitive deficits have also been identified as biotherapy side effects.[19] The type of biotherapeutic agent used may influence the type and pattern of fatigue experienced.

Many people with cancer undergo surgery for diagnosis or treatment. Despite the high incidence of postoperative fatigue observed in clinical practice, little research exists that examines causes and correlates of postoperative fatigue in people with cancer.[11] It is clear, however, that fatigue is a problem following surgery that improves with time and is compounded by fatigue experienced from other cancer treatments.[11]

Evidence suggests that anemia may be a major factor in cancer-related fatigue (CRF) and quality of life in cancer patients.[9,20,21] Anemia can be related to the disease itself or caused by the therapy. Occasionally, anemia is simply a co-occurring medical finding that is related to neither the disease nor the therapy. Anemia is often a significant contributor to symptoms in persons with cancer. For individual patients, it can be difficult to discern the actual impact of anemia, for there are often other problems that confound the ability to weigh the specific impact of anemia. The impact of anemia varies depending on factors such as the rapidity of onset, patient age, plasma-volume status, and the number and severity of comorbidities.[22] A retrospective review was conducted to understand the problem of anemia in patients receiving radiation therapy. Anemia was prevalent in 48% of the patients initially, and increased to 57% of the patients during therapy. It was more common in women than men (64% vs. 51%); however, men with prostate cancer experienced the greatest increase in anemia during radiation therapy.[23] In certain cancers, such as cancer of the cervix and cancer of the head and neck, anemia has been found to be a predictor of poor survival and diminished quality of life in patients undergoing radiation therapy.[24-27]

Fatigue often occurs when the energy requirements of the body exceed the supply of energy sources.[28,29] In people with cancer, three major mechanisms may be involved: alteration in the body’s ability to process nutrients efficiently, increase in the body’s energy requirements, and decrease in intake of energy sources. Causes of nutritional alterations are listed in the following table.

Numerous factors related to the moods, beliefs, attitudes, and reactions to stressors of people with cancer are thought to contribute to the development of chronic fatigue. Nonorganic causes comprise approximately 40% to 60% of the cases of fatigue in general medical populations, with anxiety and depression being the most common psychiatric disorders.[30]

Depression can be a comorbid, disabling syndrome that affects approximately 15% to 25% of persons with cancer.[31] The presence of depression, as manifested by loss of interest, difficulty concentrating, lethargy, and feelings of hopelessness, can compound the physical causes for fatigue in these individuals and persist long past the time when physical causes have resolved.[32] Anxiety and fear associated with a cancer diagnosis, as well as its impact on the person’s physical, psychosocial, and financial well-being, are sources of emotional stress. Distress associated with the diagnosis of cancer alone may trigger fatigue. A study of 74 early-stage breast cancer patients with no history of affective disorder, assessed various symptoms of adjustment approximately 2 weeks after diagnosis; about 45% noted moderate or high levels of fatigue. This fatigue may have been secondary to the increased cognitive strain of dealing with the diagnosis or to insomnia, reported as moderate-to-severe by about 60% of the patients. Fatigue may, therefore, begin before treatment as a result of worry or other cognitive factors, both primary and secondary to insomnia. Various forms of treatment may compound this fatigue.[33] Fatigue may also be increased in cancer survivors above that seen in the general population.[34,35] In testicular cancer survivors, anxiety and depression were predictive of fatigue, suggesting a possible role for psychiatric intervention in fatigue management.[36] (Refer to the PDQ summaries on Depression and Anxiety Disorder for more information.)

Impairment in cognitive functioning, including decreased attention span and impaired perception and thinking, is commonly associated with fatigue.[37,38] Although fatigue and cognitive impairments are linked, the mechanism underlying this association is unclear. Mental demands inherent in the diagnosis and treatment of cancer have been well documented, but little is known about the concomitant problem of attention fatigue in people with cancer. Attention problems are common during and after cancer treatment. Some of the reported attention problems may be caused by the fatigue of directed attention.[39,40] Attention fatigue may be relieved by activities that promote rest and recovery of directed attention. Although sleep is necessary for relieving attention fatigue and restoring attention, it is insufficient when attention demands are high. Empirical literature suggests that the natural environment contains the properties for restoring directed attention and relieving attention fatigue.

Disrupted sleep, poor sleep hygiene, decreased nighttime sleep or excessive daytime sleep, and inactivity may be causative or contributing factors in CRF. Patients with less daytime activity and more nighttime awakenings were noted to consistently report higher levels of CRF. Those with lower peak-activity scores, as measured by wristwatch activity monitors, experienced higher levels of fatigue.[6]

Medications other than chemotherapy may contribute to the overall sense of fatigue. Opioids used in the treatment of cancer-related pain are often associated with sedation, though the degree of sedation varies between individuals. Other medications including tricyclic antidepressants, neuroleptics, beta blockers, benzodiazepines, and antihistamines may produce side effects of sedation. The coadministration of multiple drugs with varying side effects may compound fatigue symptoms.

References

1. Blesch KS, Paice JA, Wickham R, et al.: Correlates of fatigue in people with breast or lung cancer. Oncol Nurs Forum 18 (1): 81-7, 1991 Jan-Feb.  [PUBMED Abstract]
   
   
2. Groopman JE: Fatigue in cancer and HIV/AIDS. Oncology (Huntingt) 12 (3): 335-44; discussion 345-6, 351, 1998.  [PUBMED Abstract]
   
   
3. Irvine DM, Vincent L, Bubela N, et al.: A critical appraisal of the research literature investigating fatigue in the individual with cancer. Cancer Nurs 14 (4): 188-99, 1991.  [PUBMED Abstract]
   
   
4. Hickok JT, Morrow GR, McDonald S, et al.: Frequency and correlates of fatigue in lung cancer patients receiving radiation therapy: implications for management. J Pain Symptom Manage 11 (6): 370-7, 1996.  [PUBMED Abstract]
   
   
5. Von Hoff D: Asthenia: incidence, etiology, pathophysiology, and treatment. Cancer Therapeutics 1: 184-197, 1998. 
   
   
6. Berger AM, Farr L: The influence of daytime inactivity and nighttime restlessness on cancer-related fatigue. Oncol Nurs Forum 26 (10): 1663-71, 1999 Nov-Dec.  [PUBMED Abstract]
   
   
7. Engstrom CA, Strohl RA, Rose L, et al.: Sleep alterations in cancer patients. Cancer Nurs 22 (2): 143-8, 1999.  [PUBMED Abstract]
   
   
8. Dimsdale JE, Ancoli-Israel S, Ayalon L, et al.: Taking fatigue seriously, II: variability in fatigue levels in cancer patients. Psychosomatics 48 (3): 247-52, 2007 May-Jun.  [PUBMED Abstract]
   
   
9. Glaspy J, Bukowski R, Steinberg D, et al.: Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Procrit Study Group. J Clin Oncol 15 (3): 1218-34, 1997.  [PUBMED Abstract]
   
   
10. Haylock PJ, Hart LK: Fatigue in patients receiving localized radiation. Cancer Nurs 2 (6): 461-7, 1979.  [PUBMED Abstract]
    
    
11. Winningham ML, Nail LM, Burke MB, et al.: Fatigue and the cancer experience: the state of the knowledge. Oncol Nurs Forum 21 (1): 23-36, 1994 Jan-Feb.  [PUBMED Abstract]
    
    
12. King KB, Nail LM, Kreamer K, et al.: Patients' descriptions of the experience of receiving radiation therapy. Oncol Nurs Forum 12 (4): 55-61, 1985 Jul-Aug.  [PUBMED Abstract]
    
    
13. Greenberg DB, Sawicka J, Eisenthal S, et al.: Fatigue syndrome due to localized radiation. J Pain Symptom Manage 7 (1): 38-45, 1992.  [PUBMED Abstract]
    
    
14. Nail LM: Coping with intracavitary radiation treatment for gynecologic cancer. Cancer Pract 1 (3): 218-24, 1993. 
    
    
15. Larson PJ, Lindsey AM, Dodd MJ, et al.: Influence of age on problems experienced by patients with lung cancer undergoing radiation therapy. Oncol Nurs Forum 20 (3): 473-80, 1993.  [PUBMED Abstract]
    
    
16. Fobair P, Hoppe RT, Bloom J, et al.: Psychosocial problems among survivors of Hodgkin's disease. J Clin Oncol 4 (5): 805-14, 1986.  [PUBMED Abstract]
    
    
17. Piper BF, Rieger PT, Brophy L, et al.: Recent advances in the management of biotherapy-related side effects: fatigue. Oncol Nurs Forum 16 (6 Suppl): 27-34, 1989 Nov-Dec.  [PUBMED Abstract]
    
    
18. Haeuber D: Recent advances in the management of biotherapy-related side effects: flu-like syndrome. Oncol Nurs Forum 16 (6 Suppl): 35-41, 1989 Nov-Dec.  [PUBMED Abstract]
    
    
19. Mattson K, Niiranen A, Iivanainen M, et al.: Neurotoxicity of interferon. Cancer Treat Rep 67 (10): 958-61, 1983.  [PUBMED Abstract]
    
    
20. Vogelzang NJ, Breitbart W, Cella D, et al.: Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition. Semin Hematol 34 (3 Suppl 2): 4-12, 1997.  [PUBMED Abstract]
    
    
21. Demetri GD, Kris M, Wade J, et al.: Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group. J Clin Oncol 16 (10): 3412-25, 1998.  [PUBMED Abstract]
    
    
22. Johnston E, Crawford J: The hematologic support of the cancer patient. In: Berger A, Portenoy RK, Weissman DE, eds.: Principles and Practice of Supportive Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 549-69. 
    
    
23. Bush RS: The significance of anemia in clinical radiation therapy. Int J Radiat Oncol Biol Phys 12 (11): 2047-50, 1986.  [PUBMED Abstract]
    
    
24. Fein DA, Lee WR, Hanlon AL, et al.: Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 13 (8): 2077-83, 1995.  [PUBMED Abstract]
    
    
25. Girinski T, Pejovic-Lenfant MH, Bourhis J, et al.: Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: results of a retrospective study of 386 patients. Int J Radiat Oncol Biol Phys 16 (1): 37-42, 1989.  [PUBMED Abstract]
    
    
26. Dubray B, Mosseri V, Brunin F, et al.: Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study. Radiology 201 (2): 553-8, 1996.  [PUBMED Abstract]
    
    
27. Dunst J: Hemoglobin level and anemia in radiation oncology: prognostic impact and therapeutic implications. Semin Oncol 27 (2 Suppl 4): 4-8; discussion 16-7, 2000.  [PUBMED Abstract]
    
    
28. Watanabe S, Bruera E: Anorexia and cachexia, asthenia, and lethargy. Hematol Oncol Clin North Am 10 (1): 189-206, 1996.  [PUBMED Abstract]
    
    
29. MacDonald N, Alexander HR, Bruera E: Cachexia-anorexia-asthenia. J Pain Symptom Manage 10 (2): 151-5, 1995.  [PUBMED Abstract]
    
    
30. Reich SG: The tired patient: psychological versus organic causes. Hosp Med 22 (7): 142-54, 1986. 
    
    
31. Henriksson MM, Isometsä ET, Hietanen PS, et al.: Mental disorders in cancer suicides. J Affect Disord 36 (1-2): 11-20, 1995.  [PUBMED Abstract]
    
    
32. Cella D, Davis K, Breitbart W, et al.: Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J Clin Oncol 19 (14): 3385-91, 2001.  [PUBMED Abstract]
    
    
33. Cimprich B: Pretreatment symptom distress in women newly diagnosed with breast cancer. Cancer Nurs 22 (3): 185-94; quiz 195, 1999.  [PUBMED Abstract]
    
    
34. Sugawara Y, Akechi T, Okuyama T, et al.: Occurrence of fatigue and associated factors in disease-free breast cancer patients without depression. Support Care Cancer 13 (8): 628-36, 2005.  [PUBMED Abstract]
    
    
35. Bower JE, Ganz PA, Desmond KA, et al.: Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 106 (4): 751-8, 2006.  [PUBMED Abstract]
    
    
36. Fosså SD, Dahl AA, Loge JH: Fatigue, anxiety, and depression in long-term survivors of testicular cancer. J Clin Oncol 21 (7): 1249-54, 2003.  [PUBMED Abstract]
    
    
37. Rhodes VA, Watson PM, Hanson BM: Patients' descriptions of the influence of tiredness and weakness on self-care abilities. Cancer Nurs 11 (3): 186-94, 1988.  [PUBMED Abstract]
    
    
38. Fan HG, Houédé-Tchen N, Yi QL, et al.: Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1- and 2-year follow-up of a prospective controlled study. J Clin Oncol 23 (31): 8025-32, 2005.  [PUBMED Abstract]
    
    
39. Holmes S: Preliminary investigations of symptom distress in two cancer patient populations: evaluation of a measurement instrument. J Adv Nurs 16 (4): 439-46, 1991.  [PUBMED Abstract]
    
    
40. Oberst MT, James RH: Going home: patient and spouse adjustment following cancer surgery. Top Clin Nurs 7 (1): 46-57, 1985.  [PUBMED Abstract]
    
    

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