This material is protected by U.S. copyright law. Unauthorized reproduction is prohibited. To purchase quantity reprints, please e-mail [email protected] or to request permission to reproduce multiple copies, please e-mail [email protected]. Andrea M. Barsevick, PhD, RN, AOCN®, Tracey Newhall, RN, BS, OCN®, Guidelines for the management of cancer-related fatigue (CRF) emphasize evidence-based strategies for reducing this common symptom in patients with cancer. Exercise has the largest body of data supporting its benefits in reducing CRF. Patient education and counseling also are considered integral to effective CRF management. Additional interventions can be pharmacologic or nonpharmacologic, although a combination of approaches may be employed. Several factors known to be associated with CRF may be particularly amenable to treatment. At a Glance
F Evidence supports the benefits of exercise for patients with uidelines for the management of cancer-related fatigue (CRF) are available from both the National Comprehensive Cancer Network (NCCN) (Mock et al., 2007) and Oncology Nursing Society (ONS) (Mitchell & Friese, 2007). Current NCCN recom- F Education and counseling are essential in helping patients describe four categories of consensus regarding evidence for CRF management, whereas ONS guidelines use five categories of evidence for approaches to symptom management Effective management of factors such as pain, insomnia, and (Mock et al.; Mitchell & Friese) (see Table 1). This article will fo- distress also can reduce cancer-related fatigue.
cus primarily on ONS guidelines for CRF management, although NCCN guidelines may be referred to when appropriate. The clinical status of a patient with cancer (i.e., receiving Knols, Aaronson, Uebelhart, Fransen, & Aufdemkampe, 2005; active treatment, participating in long-term follow-up, or near- NCCN, 2007; Schmitz et al., 2005; Stevinson, Lawlor, & Fox, ing end of life) will influence CRF management strategies. As 2004; Stricker, Drake, Hoyer, & Mock, 2004).
described by Piper et al. (2008) in an article beginning on page Exercise can effectively reduce CRF in various settings. Dur- 37 in this supplement, the initial fatigue evaluation is used to ing palliative care, for example, low-intensity exercise matched identify whether pain, emotional distress, anemia, insomnia, to patients’ comfort levels was associated with improved quality deconditioning, nutritional issues, or comorbidities are present. of life (Oldervoll, Kaasa, Knobel, & Loge, 2003; Porock, Krist- These factors, if present, will guide the management of moder- janson, Tinnelly, Duke, & Blight, 2000). For patients receiving ate or severe CRF (Mock et al., 2007). The current ONS fatigue marrow or stem cell transplantations, positive studies have been guidelines rate screening for and managing etiologic factors as conducted using aerobic interval training with appropriate strategies likely to be effective in fatigue management (Mitchell, monitoring (Dimeo, 2001). During chemotherapy and radiation Beck, Hood, Moore, & Tanner, 2007). Additional interventions therapy, home-based exercise programs have proven beneficial can be pharmacologic or nonpharmacologic; in many cases, a (Mock et al., 1994, 1997). Strength-resistance exercise has been used effectively in men with prostate cancer undergoing androgen-deprivation therapy (Segal et al., 2003; Stevinson et Nonpharmacologic Interventions
Carefully considering which types of exercise may be ben- for Cancer-Related Fatigue
eficial is important. The current NCCN recommendation is to Exercise
Strong evidence supports the benefits of exercise for CRF Andrea M. Barsevick, PhD, RN, AOCN®, is a director of nursing research, management. Numerous randomized, controlled clinical trials Tracey Newhall, RN, BS, OCN®, is a research nurse, and Susan Brown, have evaluated exercise during and after treatment in patients RN, OCN®, CCRP, is a research nurse, all at Fox Chase Cancer Center with various malignancies; and the data have been the subject in Philadelphia, PA. No financial relationships to disclose. (Submitted of several comprehensive meta-analyses and review articles January 2008. Accepted for publication May 1, 2008.) (Courneya & Friedenreich, 1999; Galvao & Newton, 2005; Digital Object Identifier:10.1188/08.CJON.S2.21-25 Clinical Journal of Oncology Nursing • Supplement to Volume 12, Number 5 • Management of Cancer-Related Fatigue Initiatives include planning, delegating, prioritizing activities, Table 1. Categories of Evidence
pacing, and resting. Randomized clinical trials have shown that for the Management of Cancer-Related Fatigue
patients with cancer benefited from learning energy conserva-tion (Barsevick et al., 2004). ONS guidelines describe energy CATEGoRy
conservation as likely to be effective.
Cognitive-Behavior Interventions
Distress can result in fatigue. According to NCCN guidelines, distress represents a complex, multifactorial experience that may include anxiety and depression (Holland et al., 2007; Mock et al., 2007). Complicating matters more, distress can interfere For moderate to severe distress (a score of 4 or higher on the 0–10 scale), NCCN guidelines recommend referral to a special- ist. The oncology team can provide supportive care if distress is mild (Holland et al., 2007; Mock et al., 2007).
Stress reduction and management of depression and anxiety Note. Based on information from Mitchell & Friese, 2007.
can be useful in reducing fatigue (Stark et al., 2002). Random-ized trials have shown that cognitive-behavior strategies, such as progressive muscle relaxation or relaxed breathing, may im- begin with low intensity and duration of exercise and to then prove fatigue in patients with cancer receiving radiation therapy progress slowly and modify the exercise plan as conditions or hematopoietic stem cell transplantation (Decker, Cline-Elsen, change (Mock et al., 2007). Timing, at least initially, might & Gallagher, 1992; Kim & Kim, 2005). Use of these strategies be 20- to 30-minute sessions, three to five times per week. to improve sleep also could be effective in relieving fatigue; the One study showed that patients with cancer who exercised strategies are classified by ONS guidelines as likely to be effec- more than one hour per day reported an increase in fatigue tive in reducing fatigue (Mitchell et al., 2007).
(Schwartz, Mori, Gao, Nail, & King, 2001). The appropriate Studies support the role of a cognitive-behavior approach intensity of exercise will vary depending on individual patient to improve sleep quality to reduce fatigue (Berger et al., 2003; Quesnel, Savard, Simard, Ivers, & Morin, 2003; Savard, Simard, Exercise risks and benefits should be weighed and used Ivers, & Morin, 2005). Important components of the cognitive- cautiously in patients with bone metastases, neutropenia, behavior approach include having the patient set and maintain low platelet counts, anemia, and fever. A modified exercise a schedule of regular sleep and wake times. Patients also should regimen can be recommended in some cases. For example, place themselves in an environment that is conducive to sleep a patient with neutropenia should avoid environments with and not stay in bed any longer than they intend to sleep. Caf- high infection risk, such as gyms and swimming pools (NCCN, feine, nicotine, and alcohol should be avoided, particularly in the evening or within several hours before intended sleep Exercise is the only strategy that ONS guidelines for CRF clas- sify as recommended for clinical practice. However, additional research still is needed regarding both safety and customization of exercise regimens (e.g., type, intensity, frequency, duration) Strategies for Pharmacologic
in different patient populations (Mitchell & Friese, 2007). Management of Cancer-Related
Fatigue Based on Associated Factors
Education and counseling, which should be used for all patients with cancer, are particularly beneficial for those be-ginning fatigue-inducing treatments. Data from several studies Published data suggest that the use of recombinant erythro- support the role of educational interventions (i.e., providing poietic agents (epoetin or darbopoetin) to increase hemoglobin physical sensory information, anticipatory guidance, coping levels in patients with cancer with disease- or treatment-related skills training, and coaching) to reduce CRF levels (Allison et anemia (hemoglobin < 10 g/dl) may improve vigor, fatigue, and al., 2004; Fawzy, 1995; Given et al., 2002; Yates et al., 2005). other quality-of-life outcomes (Crawford et al., 2002; Djulbegovic, Consultation may be useful regarding nutritional deficiencies 2005; Fallowfield et al., 2002; Vansteenkiste et al., 2002). Howev- that may result from anorexia, diarrhea, nausea, and vomiting er, several major concerns have arisen regarding potential risks as- associated with cancer or its treatment (Brown, 2002).
sociated with the use of recombinant erythropoietins, including Strategies that can be taught for coping with fatigue include increased risk of death, thrombotic events, red blood cell aplasia energy conservation and activity management. Energy con- (from anti-erythropoietin antibodies), and growth stimulation of servation is the deliberate and planned management of one’s certain tumor types (Rosenzweig, Bender, Lucke, Yasko, & Bruf- activities and personal energy resources. The goal is to balance sky, 2004; Stasi et al., 2005; Steensma & Loprinzi, 2005; Verhelst rest and activity so that valued activities can be maintained. et al., 2004). ONS guidelines for fatigue management emphasize October 2008 • Supplement to Volume 12, Number 5 • Clinical Journal of Oncology Nursing that clinicians and patients should carefully evaluate potential or to induce sleep. However, minimal evidence exists to support benefits and harmful effects of recombinant erythropoietins for the effectiveness of herbal supplements and concern has been individual patients (Mitchell et al., 2007).
noted regarding potential drug interactions with such agents (Berger et al., 2005; Block, Gyllenhaal, & Mead, 2004).
Emotional Distress—Depression
Pain also can be a contributing factor to fatigue. According to ONS guidelines, pain management is likely to be effective When depression has been identified as a contributing factor in reducing fatigue in patients with cancer. NCCN guidelines to fatigue, pharmacologic management of depression may be for pain in adult patients with cancer have been developed by effective in controlling CRF (NCCN, 2007). Patients may benefit experts from comprehensive cancer centers across the United from a combination of medication and counseling. Medications States. The guidelines recommend universal screening to quan- for depression include selective serotonin reuptake inhibitors, tify pain intensity and to describe the quality and anatomical tricyclic antidepressants, and monoamine oxidase inhibitors. locations. A more comprehensive pain assessment is indicated Counseling methods include behavior therapy, education, and if pain is reported (Swarm et al., 2007).
preparatory information and have been used primarily when NCCN guidelines for pain management recommend a non- fatigue was observed in association with depression, but many steroidal anti-inflammatory drug or acetaminophen (without issues surrounding the relationship between the two symptoms an opioid) or a short-acting opioid for patients with low pain and potential treatment options have not been addressed in levels (pain score of 1–3 out of 10). For moderate pain (score clinical studies and require further investigation. However, of 4–6) or severe pain (score of 7–10), an opioid may be pre- Morrow et al. (2003) and Roscoe et al. (2005) used the selec- scribed with a coanalgesic as needed. Reassessment is recom- tive serotonin reuptake inhibitor paroxetine in patients with mended every 24 hours for patients with severe pain and every cancer and found no significant effect on fatigue in the absence one to three days for patients with moderate or mild pain Sleep Disturbances and Insomnia
Future options for Management
of Cancer-Related Fatigue
ONS guidelines for pharmacologic management of sleep- wake disturbances specify that clinicians and patients should Several other agents have been used or are being evaluated carefully weigh the benefits and potential harmful effects of for the management of CRF (see Table 2). However, the efficacy pharmacologic sleep interventions (Page, Berger, & Johnson, and safety of these agents for this indication have not been 2007). In general, little research exists on the effects of sleep established (Mitchell et al., 2007). The use of psychostimulants drugs on patients with cancer; a systematic assessment is need- for fatigue is being evaluated currently in a number of research ed regarding efficacy, safety, and possible drug interactions. studies; however, more data are necessary before the use of Pharmacologic agents used for inducing sleep and improving these drugs can be recommended (Mock et al., 2007). Breitbart sleep maintenance include benzodiazepines and nonbenzodiaz- and Alici (2008) discuss investigational agents for CRF manage- epines. Other drugs prescribed for sleep disturbance manage- ment in an article beginning on page 27 in this supplement.
ment are the tricyclic antidepressants and antidepressants such as bupropion sustained release. Antihistamines, chlorohydrates, and chlorpromazine also have been used. The general recom- mendation for sleep drugs is that they not be used for more than 7–10 days (Page et al.). Many patients with cancer also use herbal CRF management strategies have been described in clinical supplements to help with side effects related to their treatment practice guidelines. Education and counseling are essential for Table 2. Potential Pharmacologic options for Cancer-Related Fatigue
Daytime sleepiness associated with narcolepsy Note. Based on information from Mitchell et al., 2007.
Clinical Journal of Oncology Nursing • Supplement to Volume 12, Number 5 • Management of Cancer-Related Fatigue helping patients with cancer anticipate and cope with fatigue the ASCO/ASH guidelines. Best Practice and Research. Clinical that may be associated with their disease or related to their Haematology, 18(3), 455–466.
cancer treatment. Effective strategies for coping with fatigue Fallowfield, L., Gagnon, D., Zagari, M., Cella, D., Bresnahan, B., Little- include energy conservation, activity management, optimizing wood, T.J., et al. (2002). Multivariate regression analyses of data from restful sleep, and relaxation techniques. Strong evidence sup- a randomized, double-blind, placebo-controlled study confirm qual- ports physical exercise as a means of reducing CRF, although ity of life benefit of epoetin alfa in patients receiving non-platinum patient limitations must be considered. Management of some of chemotherapy. British Journal of Cancer, 87(12), 1341–1353.
the etiologic factors known to be associated with CRF, including Fawzy, N. (1995). A psychoeducational nursing intervention to en- pain, insomnia, and distress, also may be effective in helping hance coping and affective state in newly diagnosed malignant to reduce these symptoms in selected patients. Effective CRF melanoma patients. Cancer Nursing, 18(6), 427–438.
management may result in improved patient quality of life.
Galvao, D.A., & Newton, R.U. (2005). Review of exercise interven- tion studies in cancer patients. Journal of Clinical Oncology, 23(4), 899–909.
Author Contact: Andrea M. Barsevick, PhD, RN, AOCN®, can be reached at
Given, B., Given, C.W., McCorkle, R., Kozachik, S., Cimprich, B., [email protected], with copy to editor at [email protected].
Rahbar, M.H., et al. (2002). Pain and fatigue management: Results of a nursing randomized clinical trial. Oncology Nursing Forum, Holland, J.V.C., Andersen, B., Breitbart, W.S., Dudley, M.M., Fleish- Allison, P.J., Edgar, L., Nicolau, B., Archer, J., Black, M., & Hier, M. man, S., Fulcher, C.D., et al. (2007). NCCN Clinical Practice (2004). Results of a feasibility study for a psycho-educational Guidelines in Oncology™. Distress management. Retrieved intervention in head and neck cancer. Psycho-Oncology, 13(7), August 20, 2007, from http://www.nccn.org/professionals/ Barsevick, A.M., Dudley, W., Beck, S., Sweeney, C., Whitmer, K., & Kim, S.D., & Kim, H.S. (2005). Effects of a relaxation breathing Nail, L. (2004). A randomized clinical trial of energy conservation exercise on fatigue in hematopoietic stem cell transplantation for cancer-related fatigue. Cancer, 100(6), 1302–1310. patients. Journal of Clinical Nursing, 14(1), 51–55.
Berger, A.M., Parker, K.P., Young-McCaughan, S., Mallory, G.A., Knols, R., Aaronson, N.K., Uebelhart, D., Fransen, J., & Aufdemkampe, Barsevick, A.M., Beck, S.L., et al. (2005). Sleep wake disturbances G. (2005). Physical exercise in cancer patients during and after medi- in people with cancer and their caregivers: State of the science cal treatment: A systematic review of randomized and controlled [Online exclusive]. Oncology Nursing Forum, 32(6), E98–E126. clinical trials. Journal of Clinical Oncology, 23(16), 3830–3842.
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Schwartz, A.L., Mori, M., Gao, R., Nail, L.M., & King, M.E. (2001). Receive free continuing nursing education credit
Exercise reduces daily fatigue in women with breast cancer for reading this article and taking a brief quiz
receiving chemotherapy. Medicine and Science in Sports and online. To access the test for this and other ar-
Exercise, 33(5), 718–723.
ticles, visit http://evaluationcenter.ons.org. After
Segal, R.J., Reid, R.D., Courneya, K.S., Malone, S.C., Parliament, M.B., entering your Oncology Nursing Society profile
Scott, C.G., et al. (2003). Resistance exercise in men receiving username and password, select CNE Listing from
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of Oncology Nursing and choose the test(s) you
Stark, D., Kiely, M., Smith, A., Velikova, G., House, A., & Selby, P. would like to take.
(2002). Anxiety disorders in cancer patients: Their nature, as- Acumentis gratefully acknowledges an educational grant from Cephalon, Inc., in support of this article. Clinical Journal of Oncology Nursing • Supplement to Volume 12, Number 5 • Management of Cancer-Related Fatigue

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