Systematic Review and Meta-Analysis of Psychological and Activity-Based Interventions for Cancer-Related Fatigue

Cancer-related fatigue has been defined as “a persistent subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning” (Mock et al., 2000). Studies suggest it is among the most common symptoms experienced by cancer patients with advanced disease and those being treated with radiotherapy and chemotherapy (Ahlberg, Ekman, Gaston-Johansson, & Mock, 2003). Furthermore, fatigue does not appear to be limited to the active treatment period. Many individuals with no clinical evidence of disease continue to experience fatigue for months or even years following treatment completion (Servaes, Verhagen, & Bleijenberg, 2002). The clinical significance of fatigue has been examined primarily in terms of its impact on quality of life. Among patients treated with chemotherapy or radiotherapy, more than one third perceived that fatigue interfered with their ability to work, relationships with others, and physical and emotional well-being (Vogelzang et al., 1997). Mechanisms involved in the development and persistence of cancer-related fatigue are only partially understood. Available evidence suggests that fatigue can occur as a consequence of metabolic changes associated with the underlying disease as well those induced by cancer treatments (Stasi, Abriani, Beccaglia, Terzoli, & Amadori, 2003). In addition, fatigue can occur as a concomitant of other common symptoms experienced by cancer patients (e.g., nausea, and pain; Stasi et al., 2003). A growing body of research also suggests that cognitive and behavioral factors may contribute to exacerbation and persistence of fatigue (Stasi et al., 2003). With regard to behavioral factors, attention has focused on the role of physical activity. Preliminary evidence suggests that cancer patients who reduce their physical activity may experience a worsening and perpetuation of fatigue due to reductions in cardiorespiratory fitness or muscle weakening (Ahlberg et al., 2003). With regard to cognitive factors, several studies have shown that the tendency to catastrophize (i.e., have negative expectations regarding one’s ability to cope with fatigue) is associated with worse fatigue (Broeckel, Jacobsen, Horton, Balducci, & Lyman, 1998; Donovan, Small, Andrykowski, Munster, & Jacobsen, 2007; Jacobsen, Andrykowski, & Thors, 2004; Jacobsen, Azzarello, & Hann, 1999). Research bearing on the management of fatigue can be divided into studies that have evaluated pharmacological or nonpharmacological approaches. In drawing this distinction, we note the lack of any studies that have formally evaluated a combination of pharmacological and nonpharmacological approaches. The current review focuses on the body of scientific evidence regarding the efficacy of nonpharmacological approaches for the management of cancer-related fatigue. As described below, previous reviews suggest this literature can be divided into activity-based interventions and psychological interventions. Activity-based interventions include professionally supervised programs and unsupervised (i.e., home-based) programs designed to promote exercise activity. Psychological interventions represent a more heterogeneous set of approaches that can include cognitive– behavioral therapy, supportive therapy, supportive-expressive therapy, and psychoeducation. To date, there has been one systematic review (Lawrence, Kupelnick, Miller, Devine, & Lau, 2004) and no meta-analysis encompassing both psychological and activity-based interventions for people with cancer. The previous review, which included studies published through 2001, sought to identify all English language articles that dealt with the assessment, occurrence, and treatment of fatigue in cancer patients. With regard to treatment studies, the search identified 10 randomized controlled trials (RCTs) assessing the efficacy of interventions for cancer-related fatigue. Although specific search items used were not described, the results of our search (described below) suggest they may have been too narrow to result in identification of all relevant studies. This earlier review identified four principal methodological concerns with the existing treatment literature. First, reporting of the basic design elements was found to be inconsistent across studies. Second, studies typically evaluated numerous endpoints without identifying those that were of primary interest and without identifying effect sizes that would be considered clinically important. Third, because endpoints were typically not defined prospectively, sample sizes in these studies were viewed as having been chosen arbitrarily. Fourth, the patient populations in several trials were quite heterogeneous with regard to cancer types and treatments. This heterogeneity was considered responsible for much of the observed variance in fatigue in these trials. With regard to the efficacy of nonpharmacological interventions, the authors concluded that the results of two trials suggested exercise (Dimeo, Stieglitz, Novelli-Fischer, Fetscher, & Keul, 1999; Mock et al., 1997) might be helpful in reducing or preventing cancer-related fatigue. The objective of this review is to provide a systematic evaluation of the efficacy of nonpharmacological interventions on fatigue in people with cancer. Toward this end, we sought to identify all RCTs of activity-based and psychological interventions conducted with adults with cancer in which fatigue was assessed as an outcome and to evaluate the efficacy of these interventions against fatigue using qualitative and quantitative methods. As part of the review, we also evaluated the methodological quality of these trials.