Fatigue is common in patients treated with chemotherapy, and it has substantial adverse physical, psychosocial, and economic consequences. Cancer-related fatigue is generally under-recognized and under-treated. Fatigue occurs on at least a few days of each month in 76% of patients treated with chemotherapy, and has been reported to occur daily in 32% of patients treated in the United States and in 24% of patients treated in Ireland. Physicians in the United States either offered no treatment or prescribed bed rest in 77% of cases, as did physicians in Ireland in 87% of cases.[1,2] Patients and their physicians are now paying closer attention to fatigue and anemia. These and other adverse events are often managed in the context of maintaining the chemotherapy dose and schedule.Discussions about fatigue and anemia generally lack the interactivity to distinguish the cause of the fatigue from other problems such as sleep disorders, poor nutrition, cancer, and depression. Patients are often reluctant to volunteer information about adverse events and will discuss them only if they are asked specifically about them. The physician or nurse generally initiates these discussions: they are usually shortless than a minuteand often only one question about fatigue is asked. In contrast, the most commonly used fatigue scale in this setting contains 13 items. Physicians do not generally use such instruments for assessing fatigue, or use only parts of them. In addition, 90% of the questions about adverse events are simple yes or no questions that cannot fully capture the patient's feelings and experiences. Furthermore, physicians often speak in words and terms that their patients cannot understand. In this article I discuss the use of erythropoiesis-stimulating proteins (ESPs) in patients with fatigue resulting from chemotherapy-induced anemia, and their effects on patients' quality of life (QOL).
Managing fatigue requires that it be properly assessed and its causes determined and treated. It is not linked solely to anemia or any other disease or cause, and it can also result from depression, pain, sleep disorders, and other conditions.[1,4] The symptoms of fatigue can be treated with pharmacologic and nonpharmacologic interventions, but many of the pharmacologic interventions, such as psychostimulants and low-dose corticosteroids, have not been thoroughly tested in the setting of fatigue. Among the nonpharmacologic interventions for cancer-related fatigue are patient education, exercise, modification of activity and rest patterns, stress management, cognitive therapies, and dietary changes.
The precise relationship between hemoglobin (Hgb) levels and fatigue is not known, but it is clear that there is a link, and fatigue is greater in persons with lower Hgb levels.[5,6] Even small increases in patients' Hgb levels can improve their fatigue and anemia-related symptoms. Instruments that measure QOL such as the Functional Assessment of Cancer Therapy-Anemia (FACT-An, consisting of the FACT-General [FACT-G] plus 13 fatigue items and 7 nonfatigue anemia-related items) can be used to discriminate patients on the basis of Hgb level and fatigue. Gabrilove and colleagues conducted a trial of epoetin alfa(Drug information on epoetin alfa) (Procrit) given once a week in patients with nonmyeloid malignancies and showed that the scores on the FACT-An were significantly higher in those with an increase in Hgb levels of 2 g/dL or more than in those with smaller increases.Cella and colleagues administered the FACT-G to patients with cancer and found that the scores on the FACT-G, as well as on the items for fatigue and nonfatigue, physical well-being, and functional well-being, were significantly better in those with Hgb levels of 12 g/dL or higher than in those with lower levels (P ≤ .02) (Table 1). These findings were confirmed in a large community trial in patients with anemia who were treated with chemotherapy and epoetin alfa, in whom the improvements in QOL measures correlated significantly with Hgb levels (r = .235; P < .001), independent of the response to chemotherapy. Cella and colleagues also administered the FACT-Fatigue (FACT-F, consisting of the FACT-G plus 13 fatigue items) (Table 2) to 375 patients with cancer and to a sample of 1,400 persons in the general population, and, as expected, fatigue was more severe and more common in the patients with cancer.
Decreasing Fatigue and Improving Quality of Life
Erythropoiesis-stimulating proteins are indicated for the treatment of chemotherapy-induced anemia, and they have been shown in clinical trials to correct or prevent anemia and to decrease the need for red blood cell transfusions. In an analysis by Cella and colleagues of pooled data from five clinical trials in patients with cancer who were treated with the long-acting ESP darbepoetin alfa(Drug information on darbepoetin alfa) (Aranesp), there was a significant correlation between increases in Hgb level and reductions in fatigue. Similarly, multivariate regression analysis of data from a randomized double-blind placebo-controlled study showed significantly greater benefits in QOL in patients treated with epoetin alfa than in those treated with placebo (Table 3).