What causes fatigue in patients with bone marrow failure disease?
The actual physiology of what happens in the body is unknown—there are lots of interesting thoughts and hypotheses on this, whether cytokine release or substrate deficiencies are part of the mechanism of action; however, we really don’t understand the cause yet. We do know that a lot of factors contribute to fatigue, including the types of cancer treatments patients may have received. We do know that patients receiving multi-modality treatments, meaning combinations of treatments, including chemotherapy, radiation, stem cell transplantation and others, tend to have more fatigue. We also know that other factors such as symptoms of depression, anxiety, uncontrolled pain, and sleep dysfunction may contribute to fatigue. In addition, other medical problems that a patient may have may also add to the fatigue burden. These may include uncontrolled hypertension, underlying heart disease or emphysema, or thyroid dysfunction (hypothyroidism).
How do you go about working with patients to help them reduce fatigue?
First, we have to get an idea of how much fatigue there really is—whether it is minimal, moderate or severe levels of fatigue. All patients should have general education about fatigue and general strategies for managing fatigue. Some general management strategies for cancer-related fatigue (CRF) include energy conservation and distraction. Examples of these include setting priorities, delegating activities, and scheduling activities at peak energy times. Distractions encompass playing games, working on puzzles and listening to music, or visiting family and friends. Those patients with more moderate or severe fatigue should undergo further evaluation in a comprehensive physical evaluation that includes a detailed history and examination. Specifi c details relating to aspects of fatigue should be reviewed in the history taking. This includes onset of fatigue, duration and frequency of fatigue, pattern of fatigue, other factors affecting fatigue, and the presence of associated symptoms (depression, sleep dysfunction, pain, anxiety, and stress). Further laboratory evaluation may be necessary to make sure other reversible medical causes are not present.
What non-drug therapies or interventions seem to work well with helping patients manage and reduce fatigue?
The best evidence for non-pharmacologic or nondrug management is activity enhancement, such as exercise, and psychosocial interventions, which are behavioral-type therapies. These interventions are recommended based on the most evidence in the literature. For the majority of patients, we try to have them start some type of exercise program. The level of exercise depends upon the patient. An individualized approach should be taken. Their level of physical activity and other underlying patient-specifi c factors may contribute to the type and intensity of exercise. Psychosocial interventions have included educational activities, support groups and individual counseling, comprehensive coping methods, stress management training and personal behavioral intervention. Some examples that may be helpful to patients with CRF include taking brief naps early in the day or listening to guided imagery tapes daily.
Is there anything a patient needs to be careful about when starting an exercise program?
Patients who have severe cardiac or pulmonary disease (heart and lung disease) or other signifi cant medical issues should consult with their provider. At times, their provider may need to do a workup to make sure it’s safe for them to exercise before prescribing an exercise program. The majority of patients should start at a very low level and increase as their stamina and conditioning get better. Patients with bone disease should be careful about exercising on hard surfaces with activities like running or jogging, because they could fracture a bone. Most patients should coordinate their activities with their provider. Certainly when their blood counts drop, and patients become more anemic, they need to adjust their activities because they may not be able to do the same level of activity during this time.
What drug therapies can help reduce fatigue?
There are some drug therapies we use to help reduce fatigue. The majority of these are stimulants. Stimulants do not have as much evidence as exercise enhancement activities or psychosocial interventions, but there are a few trials, mostly small ones in breast cancer patients. Thus far, the data is indeterminate as to whether patients may benefi t from stimulants for CRF. Further study is needed.
Another stimulant, modafi nil (Provigil®), is FDA-approved for narcolepsy and sleep disorders and has been used to treat fatigue. In addition, there is a newer long-acting stimulant, armodafi nil (Nuvigil™), that is a once a day and FDA-approved stimulant for narcolepsy and shift work disorder. For some patients, stimulants may improve their fatigue levels. Most of the evidence with stimulant use in CRF is anecdotal, although there are some small trials showing improvement. However, the jury is still out as to whether or not stimulants really have the evidence demonstrating their usefulness for the majority of patients. Antidepressants have been studied for treatment of fatigue, but studies have shown that they show improvement in fatigue only if depression is present. Therefore, antidepressants should not primarily be used to treat fatigue.
What is the most important advice you can give a patient to manage and to reduce their fatigue?
First of all, patients should try to self-monitor their fatigue, to get an idea of what makes it better and what makes it worse. Knowing what their usual activities are and correlating these with their fatigue level can be helpful when talking to their provider about fatigue and fatigue level changes associated with particular daily activities. When a new drug is started, or when the dose changes, patients should note the effect upon CRF. It would be helpful to understand whether fatigue is directly related to the treatment or other factors. Are fatigue levels related to pain or depression? It is helpful for patients to keep a diary to determine whether they can defi ne a pattern of fatigue or to note factors either improving or worsening their fatigue.
Key Points About Cancer-Related Fatigue:
- Fatigue is the most common symptom in cancer patients and may be commonly associated with other symptoms such as uncontrolled pain,depression, anxiety, sleep dysfunction, and stress.
- Patients with mild fatigue should receive information about general management strategies whereas patients with more than mild fatigue should undergo a more comprehensive evaluation.
- Treatment interventions include nonpharmacologic and pharmacologic categories. Activity enhancement (exercise) and psychosocial interventions are supported by the most evidence and are category 1 recommendations (NCCN Clinical Practice Guidelines in Oncology:Cancer-Related Fatigue).
- Stimulants may be used for CRF, although they lack data to support a category 1 recommendation (a high level of evidence from a randomized, controlled trial).
- Antidepressants should be considered only if depression is present with CRF.
Dr. Escalante is Professor and Chair of the Department of General Internal Medicine with tenure at the University of Texas MD Anderson Cancer Center. Dr. Escalante established one of the first cancer-related fatigue (CRF) clinics in the nation, and it has served as a model for other institutions
throughout the country and world. Here, she speaks about what patients can do to manage fatigue related to bone marrow failure diseases, and her remarks are directly applicable for MDS patients.