OncoLink

Cancer-Related Fatigue

Carolyn Vachani, RN, MSN, AOCN
Abramson Cancer Center of the University of Pennsylvania
Last Modified: April 3, 2013

What is Cancer-Related Fatigue?

Although healthcare professionals frequently talk about fatigue, I rarely hear a patient describe this feeling as "fatigue". Patients know it as the feeling of exhaustion, being completely worn out, unable to concentrate, feeling "heavy", and most of all, feeling more tired than they have ever felt. It is the healthcare provider who then explains that this is cancer-related fatigue.

Fatigue is one of the most common symptoms experienced by cancer patients. Studies have reported that 26 to 90% of patients experience fatigue at some time during their treatment. The reason for this large range is that the definition of fatigue has varied in these studies, as has the extent and type of tumor, and the type of treatment. In addition, fatigue is very subjective. That is, it is a personal experience, and is different for each person who experiences it. The National Comprehensive Cancer Network defines cancer-related fatigue (CRF) as "a persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning." This sense of tiredness is usually not relieved with rest and is not related to an excessive amount of activity. Many patients describe it as feeling "bone tired". They feel physically, mentally, and emotionally drained.

As you can imagine, this exhaustion has a great impact on a person's quality of life. Unfortunately, many patients see this as "par for the course" and don't seek help from their healthcare providers. On the other hand, many healthcare providers may do little more than recommend rest, which research has found is not particularly helpful. This article will review some of the interventions shown to help manage and improve CRF.

Fatigue can fluctuate during the cancer diagnosis, with "good days" and "bad days". In general, patients who are receiving chemotherapy typically have a peak in fatigue 4-5 days after treatment, or at the time when blood counts are low (nadir). For patients receiving radiation, fatigue tends to reach a peak at the end of treatment, improving anywhere from 1-3 months following therapy. These may be the normal time frames, but many patients report fatigue persisting for many months or years after therapy, even if the cancer is in remission. Patients having undergone chemotherapy, radiation therapy, and/or bone marrow / stem cell transplants, as well as those with a terminal diagnosis, often suffer the most fatigue.

What Causes Cancer-Related Fatigue?

Researchers have found several abnormalities that are related to CRF, but it is uncertain if these changes actually cause CRF or are just associated with it. There are several medical and psychosocial conditions that can either cause fatigue or increase CRF (see table 1). If it is determined that a patient has one or more of these conditions, the condition(s) should be treated first and foremost.

Table 1

Medical conditions associated with fatigue

Psychosocial conditions associated with fatigue

Anemia

Thyroid disorders

Anxiety

Pain

Nutritional deficiencies

Depression

Infection

Renal (kidney) failure

Sleep problems or deprivation

Cardiac (heart) or pulmonary (lung) disease

Lack of social support

Side effect of some medications

Poor coping skills

There are several other theories as to why cancer patients suffer from this fatigue. The first involves cytokines, which are proteins released by cells that act as a messenger for the immune system. These proteins regulate many functions of our immune system, including inflammation, immune function, and stimulating the production of all blood cells. Researchers have found that cancer causes an increase in the release of certain cytokines, and levels of these cytokines were found to be higher in people experiencing CRF, suggesting they could be a cause. It is also known that some cancers cause people to have higher "resting energy consumption", in other words they burn more calories at rest than someone without the disease, and thus require more energy to carry out daily activities. A decrease in the production of certain hormones has also been found in patients with CRF, which may contribute to the feeling of fatigue. These are all theories, and none has been proven to be the cause. In fact, it is likely there is not one single cause, but rather a combination of factors.

It is understood that a lack of physical activity can aggravate or cause fatigue. This may be because deconditioned muscles require a person to exert more energy and effort to perform a task. For this reason, exercise has been studied as a preventive measure and has been shown to work best when started before fatigue sets in, but exercise also can help to relieve fatigue associated with cancer and treatment.

How Can We Help Relieve or Prevent Fatigue?

Only two interventions have been proven truly effective in large clinical trials to relieve or prevent fatigue: correction of anemia and exercise. One reason it has been difficult to evaluate new therapies is due to a lack of understanding of the exact cause of CRF, as well as the lack of an animal model in which to do preliminary studies. You can't exactly ask a mouse to rate his fatigue! In addition to anemia and exercise, we will discuss some other ways to manage fatigue that have been shown to be helpful.

Anemia

Anemia is defined as a hemoglobin level below 12 g/dl, and symptoms include: shortness of breath or difficulty breathing with exertion, and fatigue. Anemia in a cancer patient can have many causes including: bleeding, bone marrow involvement of disease, chemotherapy, radiation therapy, organ dysfunction (heart, lung, liver or kidney disease), or nutritional deficiencies. Anemia is believed to be one factor contributing to fatigue, and its correction has alleviated fatigue in clinical trials. One way to correct anemia is through the use of blood transfusions; in some cases, this may be the best method, particularly if the patient is bleeding or having symptoms. Despite many safe guards, blood transfusions are not without risk and can lead to transmission of viruses, allergic reactions, and lung injury.

In the case of anemia that develops over the course of cancer therapy, anemia can often be corrected by stimulating the bone marrow to make more red blood cells. In our bodies, a decrease in the red blood count or hemoglobin causes the kidneys to release a protein called erythropoietin, which in turn stimulates the bone marrow to make more red blood cells. Synthetic or man-made versions of erythropoietin can also stimulate the same response. These are sometimes called growth factors, and include darbepoetin alpha (Aranesp®) and epoetin alpha (Procrit®) (other types are available in countries other than the U.S.). There are studies that have shown these growth factors are not beneficial to all cancer patients. They may increase the risk of blood clots, hypertension(high blood pressure), tumor growth, and even cause death. Therefore, your doctor will have to decide if growth factors are appropriate to treat your anemia.

In most studies, correction of anemia resulted in decreased fatigue and an increase in quality of life. It makes sense that these positive changes were greatest in patients whose tumors also responded to therapy, but studies also found that an increase in hemoglobin in those with progressive disease also resulted in improved quality of life, compared to patients with lower hemoglobin. Correction of anemia is one intervention in the treatment of fatigue, but not every cancer patient with fatigue has anemia.

Exercise

No doubt, when this intervention was first suggested, people probably thought it was ridiculous. How can you ask someone with this level of fatigue to exercise? Well, many studies have proven that exercise improves fatigue ratings and overall quality of life. People found themselves in a better mood, with more energy, feeling more rested, and better able to concentrate. Now, this does not mean running a marathon, but rather refers to light exercise, such as taking a walk, doing some simple arm exercises to lift cans of soup, marching in place, non-strenuous swimming, or pedaling on a stationary bike. Make sure your healthcare team knows of your plans and has approved the exercise. Certain exercises may not be recommended, especially for those with bone metastases, low blood counts, or other health conditions.

It is important to do something that you enjoy and start off slow then progress as you can. Most exercise study participants started before or early during the course of cancer therapy in an effort to prevent fatigue. It can be much harder to start a program once fatigue has set in, but it is not impossible. It is important to know that even if you are experiencing fatigue, even light exercise can help you feel better. Patients who are already experiencing fatigue can start with a short walk and increase the distance each day or week as you are able. It may be helpful to ask someone to walk with you as encouragement. A walk to a nice park or garden may help a person relax and take his or her mind off worries. Remember, the type of exercise is not that important; do whatever form of exercise you enjoy(that is approved by your healthcare team). The important thing is that you do some activity! You will feel much better once you get started.

Energy Conservation

Rest is commonly recommended as a way to deal with CRF, but it often does not help. One way rest can help is through energy conservation and activity planning. This is planning and saving your energy for when you want or need it most. For instance, if your son is playing in a soccer game this afternoon that you really want to go to, take it easy in the morning and conserve energy for the afternoon event. Remember that you may not have the energy to stay for an entire game, so if you want to be there until the end, go a little late.

Another way to conserve energy is to ask for help; don't be afraid to do so. I often hear from friends and family asking what they can do to help. People don't want to be in the way, but they want to be helpful, and just don't know where or when to jump in. Ask a friend to clean the house for you, prepare a meal for your family, drive the school carpool, or just sit and talk. These may seem like simple tasks, but they can be extremely helpful to someone with CRF.

Sleep problems and deprivation can add to or cause fatigue. Keep as normal a sleep schedule as possible, and talk to your doctor about options if you are unable to sleep at night. Avoid caffeine later in the day so you will be more likely to sleep at night. Avoid naps, or if not possible, limit them to 20-30 minutes and not too late in the day. See our article on insomnia for more tips.

Complementary Therapies

Mind-body interventions have been studied in the treatment of fatigue. The therapies that have shown promise include: acupuncture, healing touch, hypnosis, massage, yoga, guided imagery and relaxation. One downside to many of these therapies is the out-of-pocket expense for the patient, without a guarantee of it working. Use caution with these modalities and talk with your healthcare provider before starting them. In some areas, clinical trials studying these modalities may be available at no cost to the participant, so ask your healthcare team about it or find available trials using the OncoLink Clinical Trials Matching System.
Several fatigue management programs have demonstrated the benefits of support groups. Breast cancer patients who participated in a support group had improved mood and coping responses. Stress management was found to be helpful in studies, but interestingly, self-guided stress management was more helpful than a group-led session.

Medications

There have been studies looking at a category of medications, called psychostimulants, to relieve fatigue in patients with cancer and other diseases. These medications are meant to "stimulate" the mind and body of the patient, giving them more energy. Several small trials have found an increase in energy with the use of these medications, but they were not all tested in cancer patients. These medications include: methylphenidate (Ritalin), dexmethylphenidate (Focalin), and modafinil (Provigil). Modafinil is a medication used to treat narcolespsy. In studies with cancer patients, it was found to help those with severe fatigue, but not mild or moderate levels of fatigue. There are side effects to these medications; including loss of appetite, sleep problems, dizziness, headache and nausea. Studies continue investigating these agents. Overall, studies thus far have shown that it is best to initially treat cancer- related fatigue without medications and if non-pharmacological treatments are not helping, your healthcare team may recommend medications.

As depression and anxiety are known to contribute to fatigue, treatment with anti-depressants has been studied. This therapy was found only to be helpful in those patients suffering from true depression and not beneficial for treating fatigue in those without depression. It is normal to have a reaction of sadness to a diagnosis of cancer, but this does not always lead to depression. In fact, studies have found that only 25-30% of cancer patients meet the criteria for a diagnosis of depression.

Corticosteroids, such as dexamethasone and prednisone, have been studied and may be beneficial in the short-term for some patients. In addition to only having a short-term benefit, the side effects of long-term steroid use are a big deterrent for continuing these medications.

Clinical Trials and Specialists

Cancer-related fatigue can be the most distressing symptom for many patients, but it is not always on the top of the healthcare provider's list of problems. Nevertheless, you should not hesitate to tell your healthcare team if you are experiencing fatigue and how it is affecting your quality of life. Patients should talk with their healthcare team about treatments and interventions to help with fatigue. Inquire about clinical trials investigating fatigue. Some centers have fatigue clinics that deal with this symptom specifically. Find available trials using the OncoLink Clinical Trials Matching System.

References

Berger, A.M., Gerber, L.H., Mayer, D.K. (2012). Cancer-related fatigue: implications for breast cancer survivors. Cancer. 118(8 Suppl):2261-9. Review.

Campos, M.P., Hassan, B.J., Riechelmann, R., Del Giglio, A.(2011). Cancer-related fatigue: a practical review. Annals of Oncology. 22(6):1273-9.

Campos, M.P., Hassan, B.J., Riechelmann, R., Del Giglio, A. (2011). Cancer-related fatigue: a review. Revista da Associação Médica Brasileira. 57(2):206-214. Review.

Escalante, C.P. and Manzullo, E.F. (2009). Cancer-related fatigue: the approach and treatment.  Journal of General Internal Medicine. 24 Suppl 2:S412-6. Review.

Mitchell, S.A. (2010). Cancer-related fatigue: state of the science. PM & R: The Journal of Injury, Function, and Rehabilitation. 2(5):364-83. Review.

National Comprehensive Cancer Network, Cancer-Related Fatigue and Anemia Treatment Guidelines for Patients, Version 1.2013, March 2013.

Wanchai, A., Armer, J.M., Stewart, B.R.(2011). Nonpharmacologic supportive strategies to promote quality of life in patients experiencing cancer-related fatigue: a systematic review. Clinical Journal of Oncology Nursing. 15(2):203-14.

Wang, X.S. (2008). Pathophysiology of cancer-related fatigue. Clinical Journal of Oncology Nursing. 12(5 Suppl):11-20. Review.

More Information

Fatigue Tip Sheet: Here you will find a list of helpful tips about fatigue and cancer related anemia. You will find information that explains what fatigue is, why it happens, how it is treated, and what you can do to prevent yourself from developing it.

Fatigue Medications: Find out about medications which may be used to treat cancer related fatigue and anemia or to shorten the duration of anemia in some cancer patients receiving chemotherapy and radiation therapy.