agents may occur; therefore, ginseng must be
used with careful monitoring in selected patients.
There is not enough evidence at this time to support the routine use of ginseng in CRF.
The seed extract of the guarana plant
(Paullinia cupana) traditionally has been used
as a stimulant. An improvement in fatigue
scores was seen with the use of oral guarana
(100 mg daily) at the end of 21 days in breast
cancer patients receiving chemotherapy.101
Further studies are needed for these results to
be generalized and to understand the adverse
effects and interaction profile of guarana.
Patients who have completed cancer treatment must be monitored for fatigue over the
long term, as fatigue may exist beyond the
period of active treatment. Many studies have
shown fatigue in breast cancer survivors, and
fatigue has been demonstrated in survivors of
colorectal, lung, and prostate cancers as well as
myeloproliferative neoplasms. 28 Therefore, it is
important to screen patients for fatigue during
follow-up visits. There are currently no studies
evaluating the long-term treatment of fatigue.
In our experience, the timing of follow-up
depends on the level of fatigue and interventions prescribed. Once fatigue is stabilized to a
level with which the patient is able to cope, the
time interval for follow-up may be lengthened.
Annual visits may suffice in patients with mild
fatigue. Follow-up of patients with moderate to
severe fatigue depends on the level of fatigue,
the ability to cope, choice of treatment, and
presence of contributing factors.
CRF is a complex condition that places a signifi-
cant burden on patients and caregivers, result-
ing in emotional distress, poor functioning, and
suffering. Fatigue can occur before, during, and
long after cancer treatment. The approach to
CRF begins with screening for and educating
patients and their caregivers about the symp-
toms. Many screening scales are available that
may be used to follow patients’ progress over
time. The evaluation and management of con-
tributing conditions may help improve fatigue. If
the fatigue persists, an individualized approach
with a combination of nonpharmacologic and
pharmacologic approaches should be consid-
ered. More research is needed to understand
brain signaling pathways, cytokine changes, and
genomic changes in cancer patients with fatigue.
Though many hypotheses have been proposed,
to date there is no biological marker to assess
this condition. Biomarker research needs to be
advanced to help to identify patients at risk for
fatigue. As cytokines have a major role in CRF,
targeted therapy to block cytokine pathways may
also be explored in the future.
Acknowledgment: The authors thank Bryan
Tutt for providing editorial assistance during the
writing of this article.
1. Scherber RM, Kosiorek HE, Senyak Z, et al. Comprehensively understanding fatigue in patients with myeloproliferative neoplasms. Cancer 2016;122:477–85.
2. Neefjes EC, van der Vorst MJ, Blauwhoff-Buskermolen
S, Verheul HM. Aiming for a better understanding
and management of cancer-related fatigue. Oncologist
3. Radbruch L, Strasser F, Elsner F, et al. Fatigue in palliative
care patients—an EAPC approach. Palliat Med 2008;22:
4. Capuron L, Pagnoni G, Demetrashvili MF, et al. Basal
ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology
5. Kisiel-Sajewicz K, Siemionow V, Seyidova-Khoshknabi D,
et al. Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue. PLoS One
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