Current Research: Fatigue in Cancer

Fatigue has taken center stage as an important problem in cancer care. Most people with cancer get fatigue, either acute (short lived) or chronic during their life. Most people think fatigue that is severe or lasts a long time means that they are sick. In fact, fatigue can be a symptom of cancer. In addition, it often is a side effect of the main cancer treatments: chemotherapy, radiation therapy, biotherapy. One research study showed that between 80-96% of patients receiving chemotherapy (anti-cancer drugs) feel fatigued (Ferrell et al, 1996). 




For a long time, fatigue related to cancer didn’t receive much attention. This was because it was hard to define, and because people thought that there wasn’t much that could be done about it. Then people with cancer and their families began to tell doctors and nurses how serious it was. As people began to live longer with cancer and as treatments became more intense, sometimes the dose of treatment would have to be limited (dose limiting toxicity) if the side effect of fatigue was bad enough.

 




In the past, the most important outcome from cancer research was how long a person lived when receiving a certain treatment. Now, people with cancer have helped doctors, nurses and other members of the health care team know that it isn’t just how long you live, but how well you live that matters.


In their research study, Ferrell and colleagues (1996) showed that fatigue effects all parts of one’s life. In research studies that measure “quality of life,” fatigue is now one of the main factors that is measured. The Oncology Nursing Society held a consensus conference (a conference that brings together nurse experts from all areas of the country) a decade ago to determine what was known about fatigue, ways to manage fatigue, and to create an outline to guide nursing research in fatigue.


One example is FIRE, the Fatigue Initiative through Research and Education Project with the Oncology Nursing Society. In addition, in 1998 April was declared “Fatigue Month.” This helps give fatigue more importance and makes it more easily noticed during that month. It also helps the health care team to focus on problems and solutions having to do with fatigue.


Today, fatigue is seen as a major symptom of cancer, and major side effect of treatment. While there are already some specific ways to manage fatigue, new approaches are being studied for both people with cancer and their caregivers. Research into what fatigue is, ways to measure and manage it, and possible treatments to prevent fatigue are on-going. Hopefully, this will be the decade in which fatigue related to cancer and its treatment will be conquered!

Screening 

Most people don’t complain of fatigue unless the doctor or nurse asks, or unless their fatigue is severe. The National Comprehensive Cancer Network (NCCN) Guidelines for Cancer-Related Fatigue address this problem. Atkinson and colleagues (2000) at the University of Alabama Comprehensive Cancer Center have published the National Comprehensive Cancer Network (NCCN) Guidelines for Cancer-Related Fatigue. 


The guidelines recommend that all persons with cancer be regularly asked about fatigue by their primary cancer care team. They suggest the use of a short screening tool that asks whether fatigue causes the person distress or makes it hard to do activities of daily living. If the person has fatigue, then a more complete assessment is done in 5 areas: pain, emotional distress, sleep disturbances, anemia, and thyroid function. If a problem is found in any of these areas, then there is a treatment plan (algorithm) that can be followed. If none of the 5 areas is positive, then a more complete examination needs to be done to try to understand exactly what is causing the fatigue.

Prevention 

One of the factors that can cause fatigue is anemia. Anemia is when there is a decreased number of red blood cells whose job it is to carry oxygen to the body’s cells, and remove waste products. Anemia can often be related to chemotherapy treatments. When this happens, it can be stopped in many cases by giving a drug that stimulates red blood cell production. The drug is called epoetin alfa or erythropoietin. Erythropoietin is a substance that occurs normally in the body. It tells the bone marrow to make more red blood cells when the body has too few. Sometimes this substance is too low in the body. By taking shots of epoetin alfa, made by special laboratory techniques, the medicine can work to tell the body to make more red blood cells, and thus stop the anemia. It takes up to 8 weeks to bring the red blood cell count back up if it is low after chemotherapy, so it may be given early to prevent anemia. 

Diagnosis 

Fatigue is subjective. In other words, it is whatever the person who has it says it is. For some it’s how they feel as in, “I’m bone-tired.” For someone else it might be based on what they can no longer do. For example, “I’m too tired to get off the couch. ” In their study, Ferrell and her co-workers (1996) point out that fatigue affects a number of areas, not just one. It can affect people on the physical, emotional, intellectual and/or spiritual level. It also can vary in timing. For one person it may start shortly after chemotherapy treatment and continue till the next treatment. For another person, it may last only for a few days between treatments. 


With radiation therapy, fatigue usually begins the 2nd or 3rd week of treatment, and may last for months after radiation is finished. Fatigue with biotherapy such as interferon alpha may occur soon after starting and be related to how much medicine is being taken. (Cuaron and Thompson, 2001).


Since fatigue is hard to measure, a number of tools have been developed to help define the type and degree of fatigue. One of these, the Piper Fatigue Scale (Piper, 1993) has 22 questions grouped into 4 categories: 1) cognition (how easy it is to focus or concentrate on a subject) and mood; 2) intensity of fatigue (how much distress) and severity (ability to do activities of daily living); 3) affective (how does fatigue affect the emotions), and 4) sensory (what symptoms of fatigue are present, such as physical, mental, and emotional symptoms).

 Following the latest research trends can be confusing and overwhelming. With these Research Updates, CancerSource.com provides summaries of the latest research on screening, treatment, and diagnosis options so you can know the direction that cancer research is headed. It is important to remember that some of the tests and procedures described in this section are currently being studied for effectiveness and may not be available to the public yet.

 

 

Treatment

Atkinson (2000) states that the NCCN Practice Guidelines for Cancer –Related Fatigue can be used to manage fatigue based on the identified cause. If related to infection, problems with body fluid, abnormal blood counts, or heart problems, these can be treated, often relieving some or all of the fatigue. If the cause is anemia, then red blood cell transfusions can be given, and as appropriate, the person started on epoietin alfa to prevent further anemia. A plan should be developed that may include medicines and other (nonpharmacologic) means. For example, asking someone else to help with chores or exercising.

Pharmacologic Therapy:
Epoetin alfa: A 1998 study by Demetri and colleagues (1998) studied over 2000 patients receiving chemotherapy. It found that epoetin alfa raised quality of life scores of patients and also raised hemoglobin levels. This was not related to whether or not the tumor responded to cancer chemotherapy. Littlewood and colleagues (1999) also confirmed these findings. They studied patients in Europe and America, and found that epoetin alfa again resulted in raising hemoglobin level, as well as higher quality of life scores related to fatigue.


Psychostimulants: Medicines such as methylphenidate hydrocholoride (Ritalin®) and pemoline (Cylert®) are being studied to see if they can help reduce fatigue. One study by Breitbart and colleagues (2001) in persons with HIV infection who were experiencing fatigue showed that the people taking either of the drugs had much less fatigue than those who took a placebo (no medicine). The authors showed that not only was the fatigue less severe in those taking the medicine, but the improvement in fatigue was associated with improved quality of life, less depression, and less psychological distress. A current clinical trial (phase III) looking at the use of methylphenidate to relieve fatigue and lethargy in persons with melanoma who are taking interferon alfa can be found at http://cancertrials.nci.nih.gov.

Non-pharmacologic Therapy:
Exercise: Dr. Segal and colleagues in Ottawa, Canada studied women with Stage I or II breast cancer (a small tumor that is limited to the breast or lymph node in the armpit) who were receiving adjuvant chemotherapy or radiation therapy after surgery to kill any hidden cells. At least 80% of women receiving adjuvant therapy complain of fatigue. Dr. Segal and colleagues divided women into 3 groups: women who did self-directed exercise (walking on their own 5 days a week), women who had supervised exercise (met 3 times a week at a clinic and walked 2 days a week on their own), and women who received “usual care,” (were told to exercise if they felt well enough).


They measured physical functioning (as measured by quality of life, body weight, and aerobic capacity) at baseline and again 26 weeks later. They found a decrease in physical functioning (4.1 points) in the women receiving usual care. They found that the women in the self-directed group had an increase in functioning of 5.7 points while those women in the supervised group had only an increase in functioning of 2.2 points. They concluded that physical exercise can decrease some of the negative side effects of breast cancer treatment, including reduced physical functioning. In addition, self-directed exercise is an effective way to improve physical functioning compared with usual care. It is important to remember that any exercise plan should be discussed with your doctor or nurse before beginning to exercise.


Energy Conserving Measures: This makes so much sense that not much research has been done in this area. Much like financial resources are budgeted, energy needs to be budgeted in the person who is fatigued. Fundamental principles as defined by Donovan (2000) are prioritizing (deciding on the things that only the fatigued person can or must do), planning (deciding on the timing, as when the person feels the most energy), eliminating (is the task necessary or can it be forgotten), delegating (giving tasks that need to be done to others who can do them), modifying (can tasks be simplified so that they are easier to do?), and finally, pacing (break down tasks so that parts are done one at a time with rest in between). Specific measures to conserve energy are described in the “Managing Fatigue” section, as well as in the “Feature Articles” section. {links}

Summary

Great strides have been made in recognizing and understanding fatigue related to cancer or its treatment. Research has helped to produce guidelines and tools to help screen and manage fatigue. However, more research needs to be done to find new medicines that may help people with fatigue and to show that existing ways to deal with fatigue are effective. Finally, research can help find new and better ways to manage fatigue.

References



Atkinson A, Barsevick A, Cella D et al. NCCN Practice Guidelines for Cancer-Related Fatigue Oncology 2000;14(11A):151-161.


Breitbart W., Rosenfeld B., Kaim M and Funesti-Esch J. A Randomized, Double-blind, Placebo-Controlled Trial of Psychostimulants for the Treatment of Fatigue in Ambulatory Patients with Human Immunodeficiency Virus Disease Arch Intern Med 2001;161(3):411-420.


Cuaron L. and Thompson J. The Interferons. Chapter 5 in: Rieger, PT, ed. Biotherapy: A Comprehensive Review. 2nd ed. Sudbury, MA: Jones and Bartlett Publishers; 2001.


Demetri GD., Kris M., Wade J., Degos L., Cella D. Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: Results from a prospective community oncology study. Procrit Study Group. J Clin Oncology 2000;16(10):3412-25.


Donovan ES. What the Rehabilitation Therapies Can Do. Chapter 16 in: ML Winningham and M Barton-Burke, eds. Fatigue in Cancer: A Multidimensional Approach. Sudbury, MA: Jones and Bartlett Publishers; 2000.


Ferrell BR, Grant M, Dean GE et al. “Bone Tired:” The experience of fatigue and its impact on quality of life. Oncology Nursing Forum 1996;23(10):1539-1547.


Littlewood TJ., Bajetta E., Cella D. Efficacy and quality of life outcomes of Epoetin Alfa in a double-blind, placebo-controlled multicenter study of cancer patients receiving non-platinum containing chemotherapy. Proc Am Soc Clin Oncol 1999;abstract #2217.


Piper BF. Fatigue. In: V Carrieri-Kohlman, AM Lindsey and CM West, eds. Pathophysiological Phenomena in Nursing: Human Responses to Illness. 2nd ed. Philadelphia, PA: WB Saunders; 1993.


Segal R, Evans W, Johnson D, et al. Structured exercise improves physical functioning in women with stages I and II breast cancer: Results of a randomized controlled trial. Journal of Clinical Oncology 2001;(19)3:657-665.
 

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