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Fatigue (PDQ®): Supportive care - Health Professional Information [NCI] - Contributing Factors

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:[1,2,3,4,5,6,7,8,9]

  • Cancer treatment.
  • Anemia.
  • Medications.
  • Cachexia/anorexia.
  • Metabolic disturbances.
  • Hormone deficiency or excess.
  • Psychological distress.
  • Physical deconditioning.
  • Sleep disturbances.
  • Excessive inactivity.
  • Pulmonary impairment.
  • Neuromuscular dysfunction.
  • Pain and other symptoms.
  • Proinflammatory cytokines.
  • Nutritional deficiencies.
  • Dehydration.
  • Infection.
  • Concomitant medical illness.
  • Cardiac impairment.

Cancer Treatment

The association of fatigue with the major cancer treatment modalities of surgery, chemotherapy, radiation therapy, and biologic response modifier therapy caused speculation that fatigue resulted from tissue damage or accumulation of the products of cell death. Interest in the effects of cancer treatment on the production of proinflammatory cytokines is based on recognition of the strong fatigue-inducing effect of some biologic response modifiers such as interferon-alpha and the finding of elevated levels of proinflammatory cytokines in people experiencing persistent fatigue following cancer treatment.[10,11]

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.[12] It is clear, however, that fatigue is a problem postsurgery that improves with time and is compounded by fatigue experienced from other cancer treatments.[12]

Fatigue has long been associated with radiation exposure and is reported as being one of the most common and activity-limiting side effect of radiation therapy for cancer.[4,13] Most of the research describing the fatigue trajectory during radiation therapy has been conducted with women who have breast cancer and men who have prostate cancer.[13,14] Fatigue increases throughout radiation therapy, peaking around mid course; it remains at this level until radiation therapy is completed, improving somewhat during the 2 months after completion of treatment.[13,14,15] A study investigating the trajectory of fatigue in men (n = 82) undergoing radiation therapy for prostate cancer found significant interindividual variability.[14] The authors used hierarchical linear modeling, a highly sophisticated analytical method, to identify predictors for prolonged fatigue trajectories. Younger men with a high level of fatigue at radiation therapy initiation were at increased risk of higher levels of morning and evening fatigue during the course of radiation therapy. Additionally, level of depression at radiation therapy initiation predicted the level of morning fatigue during the course of radiation therapy.[14]

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