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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 DESCRIPTIoN
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 Education 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 DRuG ClASS APPRovED INDICATIoN
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
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Receive free continuing nursing education credit
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Clinical Journal of Oncology Nursing • Supplement to Volume 12, Number 5 • Management of Cancer-Related Fatigue
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