Since fatigue is essentially a subjective sensation, it is by nature difficult to assess. There is agreement that self-assessment should be the "gold standard." Due to the complex nature of the symptoms of fatigue, an effort to identify a set of diagnostic criteria similar to those for depression has been attempted. This syndromal approach has been useful to assess the presence or absence of the clinical syndrome of fatigue.
Table 1 summarizes the four most common measurable indices to assess fatigue. The first category in Table 1 looks at the objective function that the patient is capable of performing when subjected to a standard task. These functional tasks have limited value in cancer care, however, as they are very difficult for the advanced cancer patient to perform.
The second category in Table 1 attempts to assess the subjective effects of standard tasks.
The third category in Table 1 has been the most commonly used in oncology. The two most common scales, ECOG and Karnofsky Performance Status, consist of a physician's rating of the patient's functional capabilities after a regular medical consultation. A physical therapist completes the Edmonton Functional Assessment Tool and attempts to determine the functional status, as well as all the obstacles to clinical performance, of these patients.
The fourth category in Table 1 is the most relevant for both clinical management and clinical trials in fatigue. Visual analog scales, numerical scales, the Brief Fatigue Inventory, and the Piper Fatigue Self-Report Scale have been validated. In addition, there are validated functional assessments in most quality-of-life questionnaires.
In addition to the assessment of the intensity of fatigue, the clinical assessment of these patients requires clinicians to determine the impact of all factors on the presence of fatigue.
To treat fatigue optimally, it is vital to identify and prioritize the different underlying factors in the individual patient. Thorough records, including recent treatment history, physical examination, and medication review, in addition to simple laboratory investigations will help identify possible underlying causes. Figure 2 outlines a therapeutic approach to fatigue management in cancer patients. Whenever possible, an attempt should be made to treat these contributing factors. It is impossible to be certain whether one of these identified problems is a major contributor to fatigue or simply a coexisting problem in a given patient. Therefore, it is of great importance to measure the intensity of fatigue and the patient's performance before and after treating any contributing factor. If the level of fatigue does not improve after correction of these abnormalities, it is clear then that further treatment will not result in improvement in the future.
In patients with cancer treatment–related fatigue, it is important to exclude specific causes, such as hypothyroidism, hypogonadism, and anemia, and to consider other potential adverse effects of treatment. If specific problems are identified, they should be appropriately managed. For instance, patients with anemia may experience symptomatic improvement with the administration of erythropoietic therapy (epoetin alfa [Epogen, Procrit] and darbepoetin alfa(Drug information on darbepoetin alfa) [Aranesp]) at the dose and administration schedule that best fit the patient's need. Epoetin alfa(Drug information on epoetin alfa) may be administered weekly by subcutaneous injection; darbepoetin alfa has a longer half-life, requiring less frequent dosing. Dosages and schedules of both agents may be increased if necessary. (For up-to-date information about the safety and use of erythropoiesis-stimulating agents from the FDA, click here: information on erythropoiesis-stimulating agents (ESA), epoetin alfa (marketed as Procrit, Epogen), darbepoetin alfa (marketed as Aranesp).)
In most patients, there will be no identified reversible causes. A number of effective pharmacologic and nonpharmacologic symptomatic treatments are available for these patients.
There is substantial evidence that corticosteroids can reduce fatigue and other symptoms in cancer patients. They are probably best retained for short-term use. Their beneficial effects generally last between 2 and 4 weeks, and longer-term use carries the risk of serious adverse effects. Most studies have used the equivalent of 40 mg/d of prednisone(Drug information on prednisone).
In recent studies of terminally ill patients, megestrol (60–480 mg/d) has been shown to have a rapid (less than 1 week) beneficial effect on appetite, fatigue, and general well-being.
Psychostimulants (eg, methylphenidate(Drug information on methylphenidate), 5–10 mg in the morning and at noon or 5 mg as needed) may be of use in treating fatigue in patients with advanced cancer. The safety and efficacy of long-term methylphenidate use for fatigue have not been established. Recently, Morrow et al found modafanil (Provigil) therapy to be beneficial in mitigating fatigue, especially when used in cancer patients with severe baseline fatigue who were on cytotoxic therapy.
In addition to these agents, a number of other drugs have been tried in preliminary studies in patients with fatigue.
In a recent double-blind, randomized, controlled trial by the NCCTG, 282 patients with cancer reported improvement of cancer-related fatigue on treatment with American ginseng (Panax quinquefolius) vs placebo.
In a randomized, controlled study of 142 patients with advanced cancer conducted by Bruera et al, donepezil(Drug information on donepezil) (Aricept) was not significantly superior to placebo in the treatment of cancer-related fatigue.
Segal et al studied the effect of exercise on the fatigue experienced by prostate cancer patients receiving radiation therapy. Over 24 weeks of the 121 patients, 40 patients initiating radiotherapy with or without androgen deprivation took part in resistance exercise, 40 participated in aerobic exercise, and 41 received usual care. Results of the FACIT-F subscale showed that when compared with usual care, resistance exercise resulted in both short- and long-term improvement in fatigue and aerobic exercise resulted in short-term improvement.
Physical therapy and occupational therapy
Physical therapy may encourage increased activity, where appropriate, and provide active range of motion to prevent painful tendon retraction. Recent evidence suggests that exercise (aerobic and resistance) may reduce fatigue during chemotherapy. Assessment of the home environment by an occupational therapist can be useful. The provision of ramps, walkers, wheelchairs, elevated toilets, and hospital beds may allow the patient to remain at home in a safe environment. Education regarding the pattern of fatigue during treatment has been helpful. Counseling (more specifically, cognitive behavioral therapy) for stress management, depression, and anxiety may reduce distress and fatigue as well as improve mood.
In a recent randomized controlled trial by Cohen et al of 163 breast cancer patients receiving radiation therapy randomized to a yoga group, a stretching group, and a waitlist group, patients assigned to yoga for three 1-hour sessions a week for six weeks during radiation therapy showed improvement in fatigue (Brief Fatigue Inventory Scale [BFI] scores, 0.23) along with the stretching group (BFI, 0.45). However, the patients in the yoga group had a greater improvement in physical functioning (SF-36), compared with the stretching and waitlist groups.
Bruera E, Driver L, Barnes EA, et al: Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: A preliminary report. J Clin Oncol 21:4439–4443, 2003.
Bruera E, El Osta B, Valero V, et al: Donepezil for cancer fatigue: A double-blind, randomized, placebo-controlled trial. J Clin Oncol. 25:3475–3481, 2007
Bruera E, Strasser F, Shen L, et al: The effect of donezepil on sedation and other symptoms in patients receiving opioids for cancer pain: A pilot study. J Pain Symptom Manage 26:1049–1054, 2003.
Cleary J: The reversible causes of asthenia in cancer patients, in Portenoy R, Bruera E (eds): Topics in Palliative Care, vol 2, pp 183–202. New York: Oxford University Press, 1998.
Dimeo F, Stieglitz R, Novelli-Fischer U, et al: Effects of physical activity on the fatigue and psychological status of cancer patients during chemotherapy. Cancer 85:2273–2277, 1999.
Hann DM, Garovoy N, Finkelstein B, et al: Fatigue and quality of life in breast cancer patients undergoing autologous stem-cell transplantation: A longitudinal comparative study. J Pain Symptom Manage 17:311–319, 1999.
Henoch I, Bergman B, Gustafsson M, et al: Dyspnea experience in patients with lung cancer in palliative care. Eur J Oncol Nurs 12:86–96, 2007.
Howell SJ, Radford JA, Adams JE, et al: Randomized placebo-controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy. Clin Endocrinol 55:315–324, 2001.
Munch TN, Zhang T, Willey J, et al: The association between anemia and fatigue in patients with advanced cancer receiving palliative care. J Palliat Med 8:1144–1149, 2005.
Neuenschwander H, Bruera E: Pathophysiology of cancer asthenia, in Portenoy R, Bruera E (eds): Topics in Palliative Care, vol 2, pp 171–181. New York: Oxford University Press, 1998.
Sadler IJ, Jacobsen PB, Booth-Jones M, et al: Preliminary evaluation of a clinical syndrome approach to assessing cancer-related fatigue. J Pain Symptom Manage 23:406–416, 2002.
Segal RJ, Reid Rd, Courneya KS, et al: Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J Clin Oncol 27:344-351, 2009.
Seidenfeld J, Piper M, Flamm C, et al: Epoetin treatment of anemia associated with cancer therapy: A systematic review and meta-analysis of controlled clinical trials. J Natl Cancer Inst 93:1204–1214, 2001.