FAST FACT AND CONCEPT #173: Cancer Related Fatigue

Authors: Gary M. Reisfield, M.D. and George R. Wilson, M.D.

While several recent studies have found fatigue to be the single most prevalent, severe, and disabling symptom in cancer patients – exceeding even pain – it remains both underrecognized and poorly treated by physicians.1 This Fast Fact reviews diagnostic and treatment approaches in the palliative care setting.

Cancer-related fatigue (CRF) is a persistent sense of tiredness/diminished energy related to cancer and/or treatment, which is not relieved by rest, and which causes diminution in functional capacity and quality of life. Additional proposed ICD-10 features include: diminished concentration; diminished motivation; insomnia or hypersomnia; nonrestorative sleep; short-term memory deficits, and marked emotional reactivity to fatigue that are not primarily consequences of depression.2

CRF is often multifactorial, with biochemical, physiological, psychological, and behavioral dimensions that remain poorly defined. Assessment is aimed at identifying correctable causes and determining the impact of CRF on both patients and caregivers. Common causes of CRF include:

• Direct effect from cancer and/or treatments
• Sedating medications
• Deconditioning
• Psychiatric co-morbidities, e.g. depression, anxiety
• Hypoxemia or Severe Anemia (Hb ≤8 g/dL) and possibly moderate anemia (Hb ≤11g/dL)
• Systemic infection and/or or significant organ dysfunction, e.g. heart, liver, kidney, lung
• Electrolyte abnormalities, e.g. Na+, K+, Mg++ , Ca++
• Nutritional imbalance/impairment
• Sleep disturbance
• Uncontrolled pain

Specific Treatments : Treatment should be directed toward correcting identifiable causes, e.g. elimination of sedating drugs, correction of anemia or electrolyte imbalance.

Non-Specific Treatments: Nonspecific treatments may be helpful in reducing fatigue, optimizing function, and promoting adaptation.

Education. Educate patient/family about CRF in order to normalize the symptom and promote adaptation/adjustment through setting realistic goals; modifying and prioritizing activities; and planning activities around diurnal variations in energy levels.

Exercise. Several randomized controlled trials showed benefit of exercise in managing fatigue in patients undergoing active antineoplastic treatment.3 Aerobic exercise (low to moderate intensity; progressive) is ideal, but benefits may be realized with resistance training. A reasonable goal is 20-30 minutes of (cumulative) exercise per day, 4-5 days per week.

Drug Therapy. There is little good data for non-specific drug therapy in CRF. The following drugs have been used with variable success.

1. Psychostimulants. While there is a growing literature on the use of psychostimulants for CRF, there is a lack of good controlled trails. Methylphenidate. Small studies have shown some efficacy in CRF, but a recent RCT of methylphenidate, 5 mg po q2h prn (maximum dose: 20 mg/d) showed no difference from placebo at one week.4 Start with 2.5-5 mg and titrate as necessary to 15-30 mg po at 08:00 and noon. Modafanil. Pilot studies indicate efficacy in the treatment of fatigue associated with depression, MS, ALS, and HIV. Potentially fewer side effects than other psychostimulants. Start with 50 mg po qam and titrate as necessary to 200-400 mg po qam.

2. Corticosteroids. These may provide a modest duration of benefit (2-4 weeks) offset by the potential for significant toxicity. Reported regimens have included prednisone 7.5-10 mg po qd; dexamethasone 1-2 mg po qd; methylprednisolone 32 mg po qd.

3. Megestrol acetate. Two double-blind, crossover studies showed reduction in CRF with doses of 160 mg po tid. 5,6

References:

1. Morrow GR, Shelke AR, Roscoe JA. Management of cancer-related fatigue. Cancer Investigation 2005;23:229-239.
2. Fatigue PDQ. National Cancer Institute. www.cancer.gov/cancertopics/pdq/supportivecare/fatigue.
3. Mock V. Evidence-based treatment of cancer-related fatigue. J Natl Cancer Inst Monogr 2004;32:112-118.
4. Bruera E, Valero V, Driver L, et al. Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol 2006;24:2073-2078.
5. Bruera E, Macmillan K, Hanson J, et al. A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer. Cancer 1990;66:1279-1282.
6. Bruera E, Ernst S, Hagen N, et al. Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control 1998;2:74-78.

Fast Facts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: drosiell@mcw.edu . The complete set of Fast Facts are available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Reisfield GM and Wilson GR. Fast Fact and Concept #173. Cancer-related Fatigue. January 2007. End-of-Life/Palliative Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Purpose: Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge and Patient Care

Keyword(s): Non pain symptoms & syndromes; cancer

Specific Disease and Organ System Category(s): Cancer