Cancer-related fatigue (CRF) is a common symptom for which cancer patients often use integrative and integrative therapies; however, evidence supporting these therapies is limited. The aim of this review is to provide evidence-based recommendations for integrative interventions during and after cancer treatment for CRF. These recommendations are based on a systematic literature review from 1990 through 2019. Cognitive behavior therapy plus hypnosis and American ginseng can be considered during active treatment, and acupressure, mindfulness-based cognitive therapy, and qigong/tai chi easy can be considered during post-treatment. Coenzyme Q10 and l-carnitine are not recommended during active-treatment. All other integrative therapies for CRF had insufficient evidence to make a recommendation. While there is increasing evidence for integrative therapies for CRF, because of lack of rigorous trials and replication, no therapies could be definitively recommended. Further rigorously designed integrative therapy research is needed and should consider implementation and dissemination.
Cancer-related fatigue (CRF) is one of the most commonly reported symptoms impacting cancer survivors.1 Cancer-related fatigue is estimated to occur in up to 90% of patients during active treatment2 and 27% to 82% of patients after treatment.3 Cancer-related fatigue is defined as multidimensional and distressing fatigue related to cancer and/or cancer treatment that interferes with activities of daily living.4 It can negatively impact multiple facets of a cancer survivor’s life, resulting in decreased quality of life.1 The etiology of CRF is still unclear1; however, there is evidence that CRF is related to multiple biologic processes including the immune response, inflammation, metabolic, neuroendocrine, and dysfunction within the central nervous system, including elevations in specific neurotransmitters and metabolites.5–7 Cancer survivors with CRF may have multiple and sometimes co-occurring causes for their symptom. Along with numerous overlapping causes of CRF, distinct and clinically meaningful fatigue phenotypes have not been defined, which makes effective prevention and treatment of CRF challenging.
Exercise (aerobic and resistance training), cognitive behavioral therapy (CBT), and psychoeducational therapies are currently the only standard evidence-based recommendation to treat CRF.8 The National Comprehensive Cancer Network guidelines recommend both massage and yoga as category 1 nonpharmacological treatments for CRF.9 However, these interventions have significant limitations/barriers including access to trained providers, needed equipment, limited or no insurance coverage, cost, and scheduling.1,10–14 Additionally, both massage and yoga have very limited evidence to support their ability to treat CRF. Many pharmacological interventions, such as treatment with psychostimulants, either have not been effective or have mixed results.1,15 These factors highlight the need to identify novel interventions to treat CRF.
Many cancer patients use integrative therapies during and after cancer treatment, including treatments such as natural products (e.g., herbs and supplements) and mind-body practices (e.g., yoga, mindfulness, and acupressure). A meta-analysis of 32 surveys of cancer patients in North America found a point prevalence of 46% (95% confidence interval, 35%–56%) of integrative therapy use.16 Moreover, in cancer survivors, the experience of fatigue has been found to predict use of integrative therapies.17 Despite this high prevalence of use, information about integrative therapy use for CRF is rarely included in usual cancer care, and 62% or more of cancer survivors do not report using integrative therapies to their health care teams.18 Instead, information about these therapies comes from various sources, most often friends and family.19 These factors illustrate a great need for cancer care providers to understand the evidence base for integrative therapies for CRF management. The aim of this review is to provide evidence-based recommendations for integrative therapy interventions for CRF.
Overview of Interventions for CRF During Active Treatment
Likely to Be Effective...
American ginseng (Panax quinquefolius, Panacis quinquefolis) can be considered in people with cancer undergoing active treatment (i.e., surgery, chemotherapy, radiation; Likely to Be Effective). American ginseng is a perennial herb native to eastern North America, used as a Chinese herbal medicine. This recommendation is based on the results of 2 trials conducted in the United States in 2010 and 2014. In these studies, doses ranging from 750 to 2000 mg of powdered and encapsulated whole American ginseng root standardized to either 3% or 5% ginsenosides (Ginseng Board of Wisconsin [Wausau, Wis] and manufactured by Beehive Botanicals [Hayward, Wis]) were taken daily for 8 weeks and compared, in both studies, with matching placebo containing white rice flour. The studies recruited both cancer patients under active treatment (radiation and chemotherapy) and post-treatment, but the majority of participants were cancer patients undergoing active treatment: 265 of 364 (2014) in 1 trial and 211 of 282 (2010). The studies took place in the United States and recruited adult cancer patients with diagnoses including breast, colon, lung, prostate, gynecological, and hematological cancers. In the dose-finding pilot study,27 doses of 1000 and 2000 mg of American ginseng improved fatigue compared with placebo capsules, although these results did not reach significance. In the phase III trial using a dose of 2000 mg of American ginseng daily, at 8 weeks there was a significant improvement of fatigue by ~18% to 22% in the American ginseng group compared with 7% to 18% in the placebo group. Greater benefit was reported in patients receiving active cancer treatment compared with those who had completed treatment.15 Serious adverse events were low (approximately 3%) and did not significantly differ between groups.
Importantly, American ginseng appears not to inhibit the cytochrome p450 system28 and has not been found to impact the effects of tamoxifen, doxorubicin, cyclophosphamide, paclitaxel, 5-fluorouracil, and methotrexate, but was instead synergistic with these agents inhibiting growth in MCF-7 breast cancer cell lines.
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