Treating Cancer-Related Fatigue: The Search for Interventions That Target Those Most in Need
+ Author Affiliations
- Corresponding author: Julienne E. Bower, PhD, Psychiatry and Behavioral Sciences, University of California, Los Angeles, 300 UCLA Medical Plaza, Rm 3306, Box 987076, Los Angeles, CA 90095-7076; e-mail: jbower@ucla.edu.
© 2012 by American Society of Clinical Oncology
Fatigue is one of the most common and distressing adverse effects of cancer treatment. Up to 99% of patients experience some
level of fatigue during treatment with radiation, chemotherapy, and biologic therapies.1 Fatigue typically resolves in the year after treatment completion, but approximately 30% of patients experience more persistent
fatigue that may endure for 10 years or more.2 Fatigue is associated with decrements in all aspects of quality of life, and many patients report that they are unable to
lead a normal life because of their fatigue.3 Fatigue has also been associated with shorter recurrence-free and overall survival in patients with cancer.4 Given its prevalence and impact, fatigue is an important target for identification and treatment.
What are effective treatments for
cancer-related fatigue (CRF)? A diverse range of treatment strategies
has been evaluated,
including pharmacologic and nonpharmacologic
approaches. Indeed, a recent review of the literature indicated that
more than
170 intervention studies that have included fatigue as
a primary or secondary outcome have been conducted in patients with
cancer.5
At this point, exercise has the strongest empirical support, with
several recent meta-analyses concluding that physical activity
has a moderate beneficial effect on CRF (effect sizes
in the range of −0.30 to −0.38).6–11 There is also some support for psychological interventions, with meta-analyses showing a small to moderate beneficial effect
(effect sizes in the range of −0.10 to −0.30).10,12,13 The more modest effect sizes that were seen in the psychological studies may be a result of the fact that many did not include
a CRF-related aim or hypothesis13; the few trials that explicitly focused on fatigue, providing education about fatigue and instruction in self-care, coping
techniques, and activity management, were more effective than nonspecific interventions.14 There is more limited support for pharmacologic approaches to treating fatigue.15 Although some trials have found beneficial effects for psychostimulants,16 results are quite mixed, and a recent phase III, randomized, double-blind, placebo-controlled trial found no benefit for
methylphenidate versus a placebo in treating CRF.17
On the basis of this literature, it would be
reasonable to recommend physical activity to patients during and after
cancer
treatment (preferably under the supervision of a
rehabilitation professional) and to provide them with targeted education
about CRF. However, we do not know whether these
strategies will be helpful for patients with more severe or persistent
fatigue,
given that very few intervention studies have
specifically targeted these patients. This is particularly true for
nonpharmacologic
treatments; although trials of such treatments are
often described as interventions for cancer-related fatigue, the
presence
of fatigue is not a criterion for trial entry. Thus,
it is unclear whether the interventions examined in these studies will
be feasible and effective for those most in need. For
example, fatigue was one of the primary barriers to adherence in an
exercise trial that was conducted with survivors of
prostate cancer.18
Only a handful of randomized controlled
trials have targeted patients with moderate to severe fatigue and used
presence of
fatigue as a criterion for study entry. Results from
these studies provide preliminary evidence that psychological (cognitive
behavioral therapy19,20) and integrative medicine approaches (yoga, biofield therapy, mindfulness-based therapy21–24)
may have beneficial effects on persistent post-treatment fatigue, but
conclusions are limited by small sample sizes in several
trials. There is a critical need for larger-scale
studies that target patients with moderate to severe fatigue,
particularly
fatigue that does not remit after treatment
completion.
The article by Molassiotis et al25
that accompanies this editorial addresses this gap in the literature in
its investigation of acupuncture for post-treatment
fatigue in survivors of breast cancer. This was a
large, multicenter trial that focused specifically on patients with
moderate
to severe fatigue. The authors enrolled 302 women who
had been diagnosed with stage I to IIIA breast cancer, completed
chemotherapy,
and scored 5 or greater on a single-item 10-point
fatigue scale. The mean duration of fatigue was 15 to 18 months, with a
maximum duration of 69 months, indicating the chronic
nature of the symptom in this sample. Results showed that 6 weeks of
acupuncture, provided for 20 minutes per week, led to
significant improvements in general fatigue as assessed by the
Multidimensional
Fatigue Inventory. The intervention also led to
significant improvements in anxiety, depression, and quality of life.
Patients
in the control group received a detailed information
booklet about coping with fatigue, which was likely comparable or
superior
to what typically would be provided in the
post-treatment setting.
Findings from the study by Molassiotis et al,25 together with earlier trials,24,26
provide compelling evidence that acupuncture may be effective for
reducing CRF, at least in the short term. It will be important
to determine how enduring the effects of this
treatment are, given that only the immediate post-treatment effects were
described
in this report, and to identify the frequency and
duration of acupuncture that are necessary for improvement. In addition,
it was unclear whether fatigue levels in the
acupuncture group decreased to pretreatment levels; if not, more
intensive treatment
may be indicated. Other treatments that have been
developed for persistent CRF are more time consuming (eg, 6 months for
cognitive
behavioral therapy,19 3 months for yoga21), but these approaches also teach patients techniques that can be used after the intervention is completed, and both led
to sustained improvements in fatigue.20,21
Future trials should also compare acupuncture (and other promising
treatments) with an active control arm as well as a no-treatment
control arm to better evaluate treatment-specific
effects.
Intervention trials with fatigued patients are challenging to conduct—as noted by Molassiotis et al,25
they had to screen “many hundreds” of patients to accrue their desired
sample size—but they are vital for identifying interventions
that will work for those most in need. The study by
Molassiotis et al represents an important advance in the literature and
will hopefully motivate other investigators to
undertake conceptually driven, methodologically rigorous trials that
target
patients with moderate to severe CRF. There is also a
critical need for basic research on mechanisms underlying fatigue onset
and persistence that will guide development of
targeted therapies. In addition, determination of risk factors for
persistent
fatigue may allow us to intervene earlier with the
most susceptible patients.
For now, what advice can we offer patients
with persistent fatigue?
- Acupuncture may be helpful, particularly for
women with
nonmetastatic breast cancer, although patients should
be urged to follow the specific protocol that was found to be safe and
effective in the study by Molassiotis et al.25
-In our trial of Iyengar yoga for persistent CRF, a number of our participants had attempted other types of yoga with no relief21;
similarly, not all types of acupuncture are likely to be effective for
reducing CRF.
As more intervention studies specifically
target patients with fatigue, the range of empirically
supported treatment options for this group should expand, ultimately
leading to enhanced quality of life for the growing
population of survivors of cancer.
AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
No comments:
Post a Comment