By Rabiya S. Tuma, PhD

“I felt like an orange after all of the juice was squeezed out of it. If I went to even get myself a drink I would have to sit down,” says Eva L. Vega, who suffered from cancer-related fatigue for more than two years after having surgery and radiation in 2000 for breast cancer.

In June 2003, she told her radiation oncologist that she was worried that her cancer was coming back because she was exhausted all the time and couldn’t do anything. Her doctors couldn’t find any signs that the cancer was recurring and referred her to Carmelita P. Escalante, MD, a specialist in cancer-related fatigue at M. D. Anderson Cancer Center in Houston.

“Dr. Escalante is my angel,” says Vega. Six months after she first met Dr. Escalante, Vega, 43, follows a regimen that includes exercise to increase her energy, strategies to conserve her energy, and medication for depression. She is involved in both a cancer support group and her church.

Although not everyone may experience fatigue to such an intense degree, approximately 90% of patients are affected by cancer-related fatigue at some point during their treatment, making fatigue a more common symptom than pain or nausea. The symptom can continue for months or even years after therapy ends.

Fatigue has received more recognition as an issue for cancer patients and survivors over the past decade or so, says Dr. Escalante. Cancer treatments are now more effective and more complex and often entail several different types of therapies, including surgery, radiation, and chemotherapy. These multimodality treatments, says Dr. Escalante, improve patient outcomes but also seem to be associated with more severe fatigue. Also, with patients living longer, doctors and researchers are only now able to see the long-term impact of disease and treatment on their patients—and for some patients that seems to include fatigue.

Despite its overwhelming prevalence, however, fatigue is not a subject commonly discussed by patients and doctors, and researchers have only recently started to study the problem in depth. The good news, though, say clinicians and researchers alike, is a growing awareness of the symptom, and, once a clinician learns a patient is experiencing fatigue, options are available to help minimize or relieve the symptom. Clinical trials are ongoing to identify medications and self-management strategies that help reduce fatigue.

Understanding Cancer-Related Fatigue

The difference between cancer-related fatigue and everyday fatigue, says Paul Jacobsen, PhD, clinical program leader for the Psychosocial & Palliative Care Program at H. Lee Moffitt Cancer Center, Tampa, Florida, is that cancer-related fatigue persists and doesn’t resolve in response to rest.

“Fatigue is exacerbated by depression, emotional distress, and stress,” says Dr. Jacobsen. “And cancer patients experience high levels of stress and distress, especially during treatment, and that exacerbates their fatigue.”

Patients don’t often mention to their doctor that they are feeling fatigued because they think it is a normal part of treatment and they should just accept it, says Dr. Jacobsen. “It is the silent symptom, because patients don’t realize they are suffering a symptom.”

In some cases, patients hesitate to tell their doctors that they are feeling fatigued because they think there is nothing that can be done or they are concerned the doctors will stop or delay treatment, says Dr. Escalante.

However, both Drs. Jacobsen and Escalante emphasize that patients should talk to their doctor or nurse and not simply accept cancer-related fatigue.

Causes of Cancer-Related Fatigue

Many of the numerous causes of cancer-related fatigue can be treated. Anemia, one of the major causes, occurs when cancer drugs kill rapidly dividing cells, a population that includes not only diseased cells but also bone marrow cells that give rise to red blood cells, which carry oxygen from the lungs to the rest of the body. Without an adequate supply of oxygen, a person will feel lethargic and fatigued.

In some cases, such as with leukemias and many lymphomas, the cancer cells infiltrate the bone marrow and take up so much space that there is not enough room for the marrow to produce an adequate supply of red blood cells. Other cancers, such as breast and prostate, induce what is called anemia of chronic diseases in which molecules that normally help immune cells communicate, called cytokines, malfunction and alter the body’s iron metabolism, storage, and use, which also prevents the synthesis of enough red blood cells.

Additionally, other cancers, especially those involving the gastrointestinal tract, stomach, and colon, induce bleeding, causing an overall loss of a patient’s blood supply, which results in fatigue because the patient loses red blood cells faster than they can replace them.

Cancer can also bring about anemia if it interferes with kidney and liver function, which can cause a drop in red blood cell count. And in some cancers, such as breast, white blood cells in the marrow or in the circulating blood seem to actually destroy the red blood cells.

In mild cases, a change in diet may be adequate to relieve anemia in cancer patients. By eating more foods that contain iron and folic acid, including fruits, vegetables, and enriched grains, a person can jump-start the body’s production of hemoglobin, the molecule inside red blood cells that binds the oxygen. Even patients who already eat a healthy diet may need to alter it to compensate for the stress induced by the disease and treatments, says Linda Abbott, RN, Holden Comprehensive Cancer Center, University of Iowa.

More frequently, doctors will choose to treat anemia with a hormone called erythropoietin (EPO), which increases the production of red blood cells. Data from randomized, controlled trials show that EPO relieves anemia in a significant percentage of cancer patients and improves their quality of life relative to patients who were not treated with the drug.

The drug can be safely used during and after most cancer treatments. In some cases, it is given before symptoms of anemia appear in an attempt to prevent it from occurring.

“For patients whose fatigue is purely due to chemotherapy-induced anemia, erythropoietin can increase their hemoglobin levels, and they feel better as the levels rise,” says Dr. Escalante.

If EPO is not effective or cannot be used, a patient may be given a blood transfusion to alleviate their anemia, which will likely help with fatigue if it is due to anemia.

Cancers and cancer treatments can also affect thyroid function, which can lead to fatigue. Like anemia, doctors can treat this situation by supplementing the patient’s own hormone production with a drug.

Working Out Fatigue

In addition to EPO, exercise has been shown to improve cancer-related fatigue in randomized, controlled trials. Although this may seem counter-intuitive, excessive inactivity can cause fatigue.

“The more you reduce physical activity, the more you lose muscle mass, and therefore the more fatigued you become,” says Dr. Jacobsen. “It is a viscious cycle, and when you try to get out of it, it can be very difficult because of the lost conditioning.” In response to decreased conditioning, clinicians will often start patients on a gentle exercise plan like a walking routine or, in some cases, physical therapy.

Vega used to run three days a week before she was diagnosed with cancer, but when she first went to see Dr. Escalante, she had no energy. They agreed she would start walking a couple of times a week for a relatively short distance.

Other causes of cancer-related fatigue may not be so obvious. For example, Abbott points out that when a patient begins antitumor treatments, the body may be flooded with the debris from broken down cancer cells.

“The cells that are killed by the treatment need to be eliminated from the body.

The body then has to use energy to dispose of the old and dead cells and regenerate healthy new cells,” says Abbott. That extra energy has to come from somewhere—leaving a patient with less energy for regular activities. Sleep disturbances, emotional distress, pain, and physiological disturbances, like constipation, can also lead to fatigue. Like the need to clean up what is left behind after cancer treatment, each of these symptoms saps a patient’s energy, leaving him or her feeling tired and less able to tackle daily tasks.

Solving Cancer Fatigue

According to the experts, the first thing a patient should do when they begin to feel fatigued is talk to their doctor or nurse. Once the biological causes, such as anemia and low thyroid function, are ruled out or treated, a symptom management specialist will look for other solutions and may combine treatments.

For example, when Dr. Escalante asked Vega about her emotional distress, she found that Vega rated herself as having depression at a level of nine out of 10. So in addition to the walking program, Dr. Escalante prescribed an antidepressant.

Researchers and clinicians also find that in some patients with cancer-related fatigue, stimulants like Ritalin® (methylphenidate), which is commonly used to treat attention deficit disorder, can be helpful. This is especially true when a patient is also having trouble concentrating, says Dr. Jacobsen.

In addition to walking and taking the antidepressant, Dr. Escalante also suggested Vega carefully prioritize her activities and focus more attention on her own needs instead of trying to take care of others. By doing this, Vega says, she was able to reserve her energy for what was most important to her, and she let other people do things for her that were less important.

Delegation and prioritizing are common suggestions from the experts. If you only have a little bit of energy, it is important to make sure you use it for what you really care about, says Dr. Escalante. She often suggests that her patients get a chair for the shower or a stool with wheels for the kitchen. These relatively simple things, she says, can help a patient preserve their energy for what they really want to do, or make a hobby such as cooking possible when it otherwise would not be.

For Jan Christiansen, 61, a nurse manager at the University of Iowa hospital who is currently undergoing treatment for non-Hodgkin’s lymphoma, prioritizing has meant rearranging her work schedule to compensate for her fatigue.

Although she is still working a 50-hour week, she has had to cut back from her pre-cancer weeks that often stretched to 70-80 hours. She finds it hardest to work right after her treatments, so she makes sure to schedule them for the afternoon. She does what she has to do at work in the morning before treatment and then plans to spend the next day recuperating at home. The worst part, she says, is that her legs feel terribly heavy. “Sometimes my mind wants to go but my body doesn’t.”

Research supports the effectiveness of distraction to manage chronic pain and it may also help reduce fatigue, says Lynne I. Wagner, PhD, clinical research scientist, Branston Northwestern Healthcare, and assistant professor of psychiatry and behavioral sciences, Northwestern University, Chicago, Illinois.

“We are social creatures, and social isolation can increase depression and exacerbate fatigue.” Therefore, it’s important to keep in contact with friends and family, either visiting with them in person or by phone. Even sitting on the porch and watching what is going on in the neighborhood can reduce one’s sense of isolation, and thereby lessen the sense of distress and fatigue, she says.

Unique to the Individual

Unfortunately, both how and when fatigue affects an individual can vary, which makes it harder for doctors and patients to recognize, describe, and treat the symptom. And for some patients, it is persistent even with care.

Donna Licht, 33, was diagnosed with stage 4 non-Hodgkin’s (diffuse large B-cell) lymphoma in April 2003, and despite the fact that she is now in remission, she continues to contend with fatigue. When she first returned home from the hospital after treatment in May, she says, she would need an hour nap after going to her mailbox. After starting to exercise again, her fatigue has improved but not dissipated completely.

“I used to have a routine with a couple of naps a day,” says Licht. “I do what I used to do but more slowly. Things take me longer. To conserve my energy I don’t move as fast as I used to. I have two kids and they take a lot of energy, but I try to be active and stay happy, and that helps a lot.”

“Fatigue is like depression and cancer,” says Vega. “I heard about them but I never thought I was going to have them myself.

“The first time I saw Dr. Escalante, I sat waiting in the corner and couldn’t even look around. I was in pieces. Now, when she saw me, she said, ‘We didn’t believe it was you!’ because I have so much energy.”