Management of Fatigue
The goal of fatigue management is palliation, that is, to help the patient mitigate the effects of fatigue and, as much as possible, maximize existing energy levels. Patients should be screened for underlying treatable etiologies such as those mentioned under the "Clinical Characteristics" section.
Nonpharmacologic Interventions
General education should be provided to the patient with regard to treatment-related fatigue from chemotherapy and radiation therapy. General strategies include conserving energy; balancing rest and activity; optimizing nutrition; preventing weight loss; and using distraction such as listening to music, reading, enjoying nature, and taking 1-hour naps if needed. Teaching patients to use a diary to self-monitor their fatigue lets them see when their energy levels peak and diminish. It also provides the opportunity to plan their day accordingly. Other fatigue management interventions can be categorized into either nonpharmacologic (Table 3) or pharmacologic approaches. Nonpharmacologic interventions for CRF include patient education, exercise, energy conservation, proper nutrition and hydration, and complementary therapies such as acupuncture, cognitive behavior, and relaxation breathing. The NCCN guidelines organize the nonpharmacologic interventions into 3 categories: activity enhancement (eg, exercise), physical therapies (eg, massage), and psychosocial interventions (eg, cognitive behavioral therapy).
Activity Enhancement. Research has shown exercise to be the most effective approach for managing CRF. Based on the patient's performance status and preference, there are several exercise activities that may be beneficial, such as walking, swimming, biking, resistive exercise, aerobics, or a combination of exercises. Although studies on exercise range in frequency, intensity, and duration, empirical evidence is lacking for guidelines. Exercise should be tailored to the patient's needs to maximize its benefits. McMillan and Newhouse conducted a meta-analysis to look at the effects of exercise interventions on CRF as well as to shed light on prescriptive exercise guidelines. Electronic databases, journals, and articles were systematically searched, resulting in 16 studies representing 1426 participants (exercise = 759; control = 667). Study eligibility criteria included subjects 18 years or older, diagnosis of or treatment for cancer, exercise used to treat CRF, quantitative evaluation of the intervention, and adequate statistical data. Results showed that exercise significantly reduced CRF (P < .001). The subgroup analysis on different types of exercise demonstrated that aerobic, resistance, and mixed training interventions improved CRF, with aerobic exercise having the most significant effects (P < .001). Furthermore, exercise conducted in a supervised setting showed significant reduction in CRF as compared with unsupervised settings.
Puetz and Herring also conducted a meta-analysis to look at the effects of exercise on CRF in patients both during and after treatment to assess how much the effect is differentiated over the time of treatment and recovery. Electronic databases were systematically searched, resulting in 70 randomized control trials (43 active treatment; 27 posttreatment). Study eligibility criteria included cancer patients in active treatment or posttreatment, randomized to an exercise or nonexercise evaluation, and CRF outcome measured before, during, and/or after exercise training. Results support other studies that exercise reduces CRF in patients both during and after treatment. The overall mean effect was similar to the effects of exercise on other cancer-related outcomes such as QOL, depression, and anxiety; individual/group therapy; and pharmacotherapy. Over time during active treatment, CRF improvement varied based on the patient's baseline fatigue scores and adherence to the exercise regimen. Those with a higher adherence to exercise experienced the most improvement, even when baseline fatigue scores were low. For posttreatment, the effects of exercise on CRF were greater when the interval between the end of treatment and starting an exercise program was longer, when the exercise program was shorter in length, and when trials used a wait-list comparison. Results revealed that CRF for posttreatment patients was a predictor of exercise adherence and was more restorative, whereas for patients in active treatment, exercise was more palliative. All exercise interventions should be tailored to the patient's need, accounting for performance and physical status, and modified over the disease trajectory.
Physical therapy consultations are warranted when patients have comorbidites (eg, heart disease and chronic obstructive pulmonary disease), recent major surgery, functional/anatomic deficits, or substantial deconditioning. Use caution with patients who have bone metastasis, low platelets, anemia, fever/infection, or limitations due to metastasis or other illnesses. Occupational therapists (OTs) can be invaluable in assessing and analyzing functional problems. Specific to CRF, OTs can provide practical advice concerning energy conservation and lifestyle management. Some of the most common interventions include assessing and addressing educational needs, mobility, self-care skills, home management skills, need for assistive devices, and upper extremity strength and function. As CRF affects the patient's functional capacity, OTs can facilitate adapting activities that are meaningful yet in line with patient's current capabilities. Making sure that they have the proper equipment helps to increase the patient's independence, which, in turn, empowers them to continue making their own health care decisions and preserves their dignity as they cope with CRF.
Physical Therapies. Physical therapies include interventions such as acupuncture and massage therapy. Several studies looking at the efficacy of acupuncture for CRF have demonstrated clinical significance, but more randomized control studies are needed with larger sample sizes to demonstrate statistical significance. A recent study conducted by Johnston et al looked at patient education with acupuncture for relief of CRF. This was a randomized controlled feasibility study. Thirteen participants (7 control, 6 treatment) were women, were considered free of breast cancer (after treatment), and had a fatigue rating of 4 or higher on the Brief Fatigue Inventory. Part 1 of the intervention entailed educating patients to improve self-care through exercise, nutrition, and cognitive behavioral techniques (4 weekly 50-minutesessions of stress management). In the second part of the intervention, patients received 8 weekly 50-minute acupuncture sessions. Results showed positive but not statistically significant results. Mean (SD) CRF scores at baseline were 6.33 (1.39) for the treatment group and 6.00 (1.09) for the control group. After 10 weeks of treatment, scores were 2.13 (1.23) and 4.38 (2.53) for the treatment and control groups, respectively. The treatment group experienced a 2.38-point decline (66%) in CRF as compared with the control group. Although the results of this study were not statistically significant, they were clinically significant.
Several massage studies show clinical significance, but similar to acupuncture, more large-scale randomized control trials are needed for statistical significance to confirm efficacy. One randomized control study (N = 86) looked at the efficacy of classical massage treatment for reducing symptoms related to breast cancer and improving mood. Women with primary breast cancer were randomized into either the massage group or the waiting list. The intervention group received biweekly 30-minute classical massages in the back and neck area twice a week for 5 weeks. The control group did not receive additional treatment beyond usual care. Each intervention participant completed questionnaires at baseline (T1), at the end of intervention (T2), and at 11 weeks follow-up (T3). Results showed a reduction in fatigue at the end of the intervention, which was sustained over time and was statistically significant compared with the control group at week 11. If massage can be proven in larger studies to be effective for reducing CRF, it could be used as an additional intervention to medication and physical activity.
Psychosocial Therapy. Cognitive behavioral therapy teaches patients to understand how thoughts can influence their feelings and behavior. They are taught to recognize and identify thought patterns and behaviors when they occur and to use cognitive coping skills to modify them. Unlike cognitive behavioral therapy, which teaches patients to modify the meaning or content of negative thoughts, mindfulness-based cognitive therapy teaches patients to use a detached perspective to avoid the escalation of negative thought patterns. A recent study (N = 100) looked at the effectiveness of mindfulness-based cognitive therapy in reducing CRF in cancer survivors of mixed diagnoses. Patients were randomized to either the intervention (n = 59) or the wait-list (n = 24) group. Fatigue severity was determined using the subscale of the Checklist Individual Strength tool. Questionnaires were completed at baseline and at the end of the 9-week intervention. The intervention group received a 6-month follow-up. The intervention group received 9 weeks of a protocolized group therapy that included 8 weekly sessions lasing 2.5 hours, one 6-hour session, and one 2.5-hour follow-up session 2 months after the ninth session, for a total of 28.5 hours. Results revealed a positive effect on CRF as the primary outcome variable. The mean fatigue score at postmeasurement was significantly lower in the intervention group (95% confidence interval, 33.2–37.9) than in the wait-list group (95% confidence interval, 40.0–47.4), controlling for pretreatment fatigue levels. Kwekkeboom and colleagues found similar positive results in a review of 43 studies on mind-body interventions. Along with coping skills training and imagery/hypnosis, cognitive behavioral therapy has improved the cancer-related symptoms of pain, fatigue, and sleep disturbance.
Nutritional Consultation
It is beyond the scope of this article to address the many issues that cancer patients experience affecting their nutrition which, in turn, adds to their CRF. Nutrition consults are needed to deal with the complexities interfering with dietary and fluid intake resulting from the cancer itself, treatments, and adverse effects of treatment.
Pharmacologic Interventions
Although several medications have been used to reduce CRF, larger randomized control trials are needed to rigorously evaluate their effectiveness in patients with CRF. The most commonly used medications in treating CRF are psychostimulants (methylphenidate and modafinil), antidepressants (paroxetine and bupropion), and cholinesterase inhibitors (donepezil). Less commonly used medications include corticosteroids and hematopoietic growth factors. Methylphenidate has been reported to improve QOL, reduce CRF, and along with exercise, increase functional capacity. Appropriate adult dosing for this drug is 10 to 60 mg daily in 2 to 3 divided doses preferably 30 to 45 minutes before meals. Maximum dose is 60 mg/d. Dose may be limited by adverse effects. Modafinil was originally approved for the treatment of narcolepsy and is currently the drug of choice for multiple sclerosis. It works in the central nervous system by facilitating release of the neurotransmitters dopamine, norepinephrine, and serotonin, promoting wakefulness. The starting dose of this drug for adults is 200 mg daily in the morning. The maximum dose is 400 mg/d.
Antidepressants such as paroxetine and sertraline (selective serotonin reuptake inhibitor) have not shown to be effective in relieving CRF. Bupropion is a norepinephrine dopamine reuptake inhibitor that may act as a stimulant and has provided significant improvement for depression and CRF. The starting dose for adults is 100 mg daily for 3 days, then the dose is increased to 100 mg 3 times daily at least 6 hours apart. Maximum dose is 450 mg/d in 3 divided doses. Donepezil, a reversible acetylcholinesterase inhibitor used in treating patients with Alzheimer disease, has shown promise for CRF. The half-life is prolonged at 70 hours with a plasma protein binding of 96%. Starting dose is 5 mg daily at bedtime, with dose increased to 10 mg daily after 4 to 6 weeks. Maximum dose is 23 mg daily after 3 months. Corticosteroids have been used to treat CRF and increase energy levels on a short-term basis. The NCCN also recommends using corticosteroids for patients at the end of life but only after ruling out other causes of CRF. Another medication that has been used for CRF is hematopoietic growth factors. However, due to the higher mortality rates and propensity for thromboembolic events, they are not frequently used and have been pulled from drug trials due to safety concerns. Other medications have been used to treat CRF without consistent efficacy, but the NCCN has now included the consideration of psychostimulants for CRF after other causes have been ruled out.