Toward Development of Guidelines for Managing Fatigue

FORT LAUDERDALE, Fla--It is difficult to develop guidelines for managing fatigue in cancer patients because of what David Cella, PhD, termed a "shameful lack of research in this area." At its third annual conference, the National Comprehensive Cancer Network (NCCN), a coalition of 16 leading US cancer centers, invited Dr. Cella to offer suggestions on how such guidelines might be formulated.

Dr. Cella, director of the Center on Outcomes, Research, and Education at Evanston Northwestern Healthcare, said that the problem of writing guidelines for fatigue management starts with the lack of a basic definition of fatigue. Dr. Cella is proposing a specific set of diagnostic criteria (see table), but, in general, fatigue is defined as a "self-recognized state of overwhelming sustained exhaustion and decreased capacity for physical and mental work, not relieved by rest."

Fatigue greatly affects quality of life. "Patients see it as a time stealer, something that wastes away their day," he said. This inability to do things can create a loss of self-esteem and lead to social isolation, depression, and, in some cases, a loss of hope about overcoming the cancer or dealing with the treatment. "So the problem of fatigue reverberates and ripples into all areas of life," Dr. Cella said.

Fatigue is widely prevalent among cancer patients and is considered by many to be a greater problem than cancer-related pain. In a survey, 74% of patients said that fatigue had been a problem over the past week versus 60% who said that pain had been a problem.

The Fatigue Coalition Survey of 600 cancer patients, 200 medical oncologists and radiation oncologists, and 200 caregivers showed that 78% of patients reported fatigue (defined as a debilitating tiredness or loss of energy at least once a week), with 32% reporting fatigue daily. Of the patients reporting fatigue, 71% said that it significantly or somewhat impaired their daily routine.

In contrast, although the oncologists recognized the prevalence of fatigue, they underestimated its effects. Only 37% said they believed that fatigue has more of an effect on quality of life than pain, compared with 60% of patients, and only 27% of the oncologists said they had ever recommended treatment for fatigue. "So the clinical activity is lower than the awareness of the problem," Dr. Cella commented.

He noted that anemia is a common, and treatable, cause of fatigue. Patients with low hemoglobin levels (below 12) tend to score about 15 points lower on quality of life scales than those with higher hemoglobin levels, he said.

Dr. Cella also reviewed data suggesting an association between cytokine levels (primarily IL-1, IL-2, IL-3, IL-6, TNF, and interferon) and fatigue. "We know that the administration of interferon produces a debilitating fatigue and that the administration of a TNF (tumor necrosis factor) blocker reduces fatigue in patients with congestive heart failure," he said. Thus, use of cytokines as anticancer therapy may be contributing to the problem of fatigue.

In a pilot study at Evanston Northwestern Healthcare, Dr. Cella and his colleagues are tracking changes in cytokine levels and fatigue levels in early-stage breast cancer patients undergoing localized radiation therapy to look for a possible association.

Physicians may not recognize, or attempt to treat, fatigue because, as Dr. Cella pointed out, "patients are very sheepish about talking about fatigue for a variety of reasons." Patients may feel that treatment of fatigue is futile or may be associated with side effects; they may want to be a "good patient" who doesn’t complain or distract their physician from what they consider their "real problem"--the cancer. Or they may not want to hear bad news, fearing that the fatigue means the cancer is progressing.

The Fatigue Coalition has promoted efforts to include cancer-related fatigue in the diagnostic nomenclature used for reimbursement purposes, "and we’ve actually gotten approval for it to go into ICD-10," Dr. Cella said, which means that the term must be better defined. A Fatigue Coalition subgroup working on this problem has put together a draft proposal for diagnostic criteria (see table).

Finally, in terms of management of fatigue, he emphasized that first, the physician should look for underlying causes that may be treatable, such as dehydration, electrolyte imbalance, vitamin deficiency, medication interaction, anemia, and depression.

He also offered energy conservation tips physicians can pass on to their patients: Identify energy-depleting activities and reduce them. Preschedule and prioritize activities. Delegate responsibility to others to do things that are less important to the patient’s sense of self and self-esteem. Achieve adequate sleep and rest.