UICC World Cancer Congress 2006

Objectives: The objectives of this presentation are to review the current state of the knowledge of the prevalence, correlates, and mechanisms of fatigue in people with cancer, critically evaluate gaps in current knowledge, and discuss the application of current knowledge to the care of people with cancer.

Methods: This presentation is based on a systematic review of published research on the prevalence, correlates, and mechanisms of fatigue between 1975 and present, abstracts from selected conferences, and currently funded studies indexed in the U. S. CRISP database and the International Cancer Research Portfolio.

Results:

Fatigue is the most common side effect of cancer treatment, reported by 50-90% of people receiving chemotherapy, radiation treatment, and selected biologic response modifiers during treatment. There is limited information about the prevalence of fatigue following specific types of cancer surgery, with hormone manipulation or targeted therapies, as a symptom of advanced cancer, or as a presenting symptom of cancer. Although several different demographic and clinical variables such as age, gender, employment status, social resources, comorbid conditions, cancer diagnosis, stage of disease, and phase of the cancer experience (diagnosis, treatment, long-term survivorship) have been examined as possible correlates of fatigue, findings across studies are often inconsistent. Some differences are apparent in head-to-head comparisons of different treatment regimens for the same type and stage of cancer. These differences indicate that there are higher levels of fatigue with more intense/high dose chemotherapy treatment regimens and that fatigue is a dose limiting side effect of treatment with high dose interferon alpha. In general, fatigue increases from diagnosis through the end of a course of radiation treatment or the last cycle of chemotherapy and gradually declines in the weeks and months following completion of these treatments. However, a subset of people experience various levels of persistent fatigue following treatment. The prevalence of long-term post-treatment fatigue is not well established. In studies of women following breast cancer treatment, overall prevalence of persistent fatigue ranges from 10% to 20%.

There are few studies that address mechanisms of fatigue as a side effect of treatment. The only well established mechanism is chemotherapy-induced anemia. Since the relationship between chemotherapy-induced anemia and fatigue is based upon the findings of studies examining the effects of treating chemotherapy-induced anemia with erythropoietic agents, there is little information about the relationship between fatigue and decreasing hemoglobin levels. Other potential mechanisms for fatigue in people with cancer being examined in humans include hormone changes, depression, induction of proinflammatory cytokines, central nervous system changes, sleep disruption, declines in aerobic capacity, and muscle wasting. Additional proposed mechanisms include dehydration, accumulation of products of cell death, nutritional deficits, side effects of medications other than cytotoxic drugs or biologic response modifiers, anxiety, cognitive demands, and overall life demands. Most of the proposed mechanisms are discussed in the literature in relation to fatigue experienced during treatment. The extent to which these same mechanisms are likely to apply to persistent fatigue is not clear. The independent contributions of cancer and cancer chemotherapy to fatigue are being examined in an animal model.

Current knowledge of the prevalence, correlates, and mechanisms of fatigue in people with cancer has implications for several areas of cancer care such as identifying people at high risk; timing fatigue assessment and preparatory information interventions; establishing a plan for preventive action; and addressing the needs of cancer survivors following the completion of treatment. Further research on mechanisms will lead to additional strategies both for preventing and managing fatigue in people with cancer.