Nonpharmacological Interventions in the Treatment of Cancer-Related Fatigue

Background: Cancer-related fatigue is the most common complication in patients. Astragalus membranaceus is widely used in many countries to treat cancer, but its efficacy and safety is uncertain. Objectives: This study aimed to summarize the evidence on Astragalus membranaceus on cancer-related fatigue and quality of life in patients with cancer. Methods: Nine electronic databases were explored for the clinical randomized controlled trial of intervention with Astragalus membranaceus alone for cancer-related fatigue and quality of life in cancer patients from inception to July 1, 2022. The risk of bias assessment tool was adopted by Cochrane Handbook 6.1.0. The effect size was estimated using relative risk and mean difference with a corresponding 95% confidence interval. Review Manager 5.4 was used for meta-analysis. The evidence level was assessed using Grading of Recommendation, Assessment, Development and Evaluation (GRADE). Results: Eight studies were included. The results of the meta-analysis showed that the addition of Astragalus membranaceus to the control group was effective in reducing cancer-related fatigue (SMD = -1.63, 95% CI [-1.90, -1.36], P < .00001) and (RR = 1.55, 95% CI [1.19, 2.02], P = 0.001) in patients with cancer and improving quality of life (SMD = 0.86, 95% CI [0.17, 1.55], P = 0.01) and (RR = 1.57, 95% CI [1.10, 2.23], P = 0.01). Conclusion: The current evidence is supportive of the efficacy of Astragalus membranaceus in patients with cancer-related fatigue and their quality of life, but due to the small and low quality of the included literature and the lack of uniformity in terms of cancer type as well as treatment modalities, there is currently insufficient evidence to provide strong support for the clinical use of Astragalus membranaceus in the treatment of cancer-related fatigue. More high-quality evidence is needed in the future to further validate the use of Astragalus membranaceus in the treatment of clinical cancer-related fatigue. Registration: A review protocol was developed and registered in the International Prospective Register of Systematic Reviews (PROSPERO). Registration number: CRD42023442277. Registered 20 July 2023.

Cancer-related fatigue (CRF) is a very common and distressing symptom experienced by most cancer patients, during and after treatments and also at the end of life. There is no accepted definition of CRF, because it is a multifaceted symptom that involves multiple biopsychosocial aspects. Several scales for assessing CRF have been used, unidimensional or multidimensional, but there is no agreement regarding the best instrument to measure CRF. Concerning the CRF treatment, pharmacologic and non-pharmacologic interventions have been used. Pharmacologic therapies have been evaluated in few randomized clinical trials: corticosteroids demonstrated a superior efficacy to the placebo in terminal cancer patients; psychostimulants (methylfenidate, dexamphetamine, modafinil), antidepressant (paroxetine), acetilcholinesterase inhibitors (donepezil), l-carnitine and coenzyme Q(10) generally have reported negative results. Non-pharmacologic interventions (physical exercise, psychosocial interventions and other integrative interventions, such as yoga, ginseng, acupuncture) have been evaluated in several randomized and non-randomized studies, but with many methodological limitations. Therefore, the most effective non-pharmacological intervention remains unclear and the effect sizes are small. Further research is needed to delineate the optimal definition, measurement and treatment of CRF.

Backgrounds:Cancer-related fatigue (CRF) is one of the most common and disabling outcomes in patients with breast cancer (BC). Traditional Chinese medicine (TCM) nonpharmacological interventions are becoming increasingly popular for cancer treatment and rehabilitation interventions. However, their efficacy and safety remain unclear and there is no systematic review or meta-analysis focusing fully on this issue. We aim to evaluate the effects of representative TCM nonpharmacological interventions, including Qigong, Tai Chi, acupuncture, and Tuina, on CRF in BC patients.Methods:Published randomized controlled trials (RCTs) that assessed the efficacy of these interventions on CRF for BC patients will be included. We will search from the following electronic databases: PubMed, Cochrane Library, EMBASE, MEDLINE, Web of Science, Scopus, PsycINFO, PSYINDEX, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang Database, and Chinese Biomedical Literature Database (CBM). The primary outcomes are the improvement of CRF, which will be evaluated by the Piper Fatigue Scale (PFS), the Functional Assessment of Cancer Therapy (FACT)-Fatigue Scale, Schwartz Cancer Fatigue Scale (SCFS), the Multidimensional Fatigue Inventory (MFI). The secondary outcomes are quality of life and safety. The meta-analysis will be performed using RevMan ver 5.3(Cochrane) statistical software.Results:We will provide more practical results investigating the efficacy of Qigong, Tai Chi, acupuncture, Tuina for BC patients with CRF from several respects including the improvement of fatigue, quality of life, and safety.Conclusions:This review will generate more stronger evidence in BC patients for TCM nonpharmacological interventions, including Qigong, Tai Chi, acupuncture, Tuina, in the treatment of CRF and help to inform clinicians and policymakers.Ethics dissemination:Ethical approval is not necessary because all of the study base in our review will be based on published research. We will submit our results to a peer-reviewed journal.Study registration number:The study is priorly registered through International Platform of Registered Systematic Review and Meta-analysis Protocol on October 2, 2020 (INPLASY 2020100003)

Cancer-related fatigue is a symptom of cancer where most patients or the general practitioners tend to misinterpret due to the insufficient understanding or knowledge of cancer-related fatigue (CRF). This paper will provide a better perspective for the patients and the health professionals on how to manage and handle CRF for both mild and severe fatigue patients. Articles were selected from the searches of PubMed database that had the terms "randomized controlled trials," "cancer," "fatigue," "pharmacologic treatment," and "nonpharmacologic treatment" using both Mesh terms and keywords. The authors have reviewed the current hypothesis and evidence of the detailed etiology of the CRF present in the literature for healthier management, directives, and strategies to improve the treatment of cancer-related fatigue. An algorithm has been blueprinted on screening, and management, of the CRF, and various kinds of effective treatments and assessment tools have been briefly studied and explained. Although many strategies seemed promising, the quality of randomized controlled trials is generally quite low in studies, making it difficult to draw conclusions about the effectiveness of each self-care strategies. Therefore, future studies require better design and reporting of methodological issues to ensure evidence-based self-care recommendations for people receiving cancer treatment.

This review assesses the efficacy of Open Label Placebos (OLPs) for the treatment of Cancer Related Fatigue (CRF) and the methodological challenges of such trials. We included randomized controlled trials comparing OLPs to treatment as usual or waitlisted controls in adults (≥ 18years) with moderate CRF. Eligible participants included cancer survivors and advanced cancer patients. We searched PubMed, MEDLINE, and Cochrane databases on July 12, 2025. Risk of bias (ROB) was assessed using the Cochrane ROB2 tool. Results were synthesized narratively due to heterogeneity. Quality of evidence was assessed for the use of OLPs for the treatment of CRF in cancer survivors using the GRADE approach. Three RCTs (total N = 87) met inclusion criteria, two studied the changes in cancer survivors, one studied advanced cancer patients. All trials had high ROB, particularly due to the lack of blinding of assessors (patients) and the use of patient-reported outcomes. All studies reported CRF improvement in the OLP arms. Two showed significant reductions in fatigue compared to controls. The quality of evidence was found to be very low. Though an overall positive effect is seen, the evidence supporting OLPs for CRF is of very low quality. This is mostly due to methodological challenges seen in trials using patient-reported outcomes where the participants can discern their allocation. Larger, methodologically robust studies are needed to clarify OLP efficacy. Functional fatigue scales, in place of patient-reported outcomes, may reduce bias in future trials. PROSPERO CRD42024449166.

Cancer-Related Fatigue: State of the Science

This is an updated version of the original Cochrane review published in issue 1 2008 (Minton 2008). Cancer-related fatigue (CRF) is common, under-recognised and difficult to treat. There have been studies looking at drug interventions to improve CRF but results have been conflicting depending on the population studied and outcome measures used. No previous reviews of this topic have been exhaustive or have synthesised all available data. To assess the efficacy of drugs for the management of CRF. We searched the Cochrane Central Register of Controlled Trials (from Issue 2 2007) MEDLINE and EMBASE from January 2007 to October 2009 and a selection of cancer journals. We searched references of identified articles and contacted authors to obtain unreported data. Studies were included in the review if they 1) assessed drug therapy for the management of CRF compared to placebo, usual care or a non-pharmacological intervention in 2) randomised controlled trials (RCT) of 3) adult patients with a clinical diagnosis of cancer. Two review authors independently assessed trial quality and extracted data. Meta-analyses were performed on different drug classes using continuous variable data. Fifty studies met the inclusion criteria. Six additional studies were identified since the original review. Only 31 of these studies involving 7104 participants were judged to have used a sufficiently robust measure of fatigue and thus were deemed suitable for detailed analysis. The drugs were still analysed by class (psychostimulants; haemopoietic growth factors; antidepressants and progestational steroids). Methylphenidate showed a small but significant improvement in fatigue over placebo (Z = 2.83; P = 0.005). Since the publication of the original review increased safety concerns have been raised regarding erythropoietin and this cannot now be recommended in practice.There was a very high degree of statistical and clinical heterogeneity in the trials and the reasons for this are discussed. There is increasing evidence that psychostimulant trials provide evidence for improvement in CRF at a clinically meaningful level. There is still a requirement for a large scale RCT of methylphenidate to confirm the preliminary results from this review. There is new safety data which indicates that the haemopoietic growth factors are associated with increased adverse outcomes. These drugs can no longer be recommended in the treatment of CRF. Readers of the first review should re-read the document in full.

Despite the high prevalence of cancer-related fatigue and its documented negative effects on patients' quality of life, limited evidence is available to support interventions to prevent or treat cancer-related fatigue. Both pharmacologic and nonpharmacologic interventions have been tested, with aerobic exercise programs and anemia correction by erythropoietin demonstrating greatest effectiveness. This article reviews the available evidence and describes gaps in knowledge. Recommendations for future research on interventions for cancer-related fatigue are presented.

Cancer-related fatigue (CRF) is the most commonly reported symptom in patients with cancer with a prevalence up to 100%. It has a signifi cant negative impact on quality of life. An effective management of CRF could signifi cantly reduce the disease burden associated with cancer and its treatment. Unfortunately, the underlying pathophysiology is very complex and not uniform.This article reviews the possible therapy of contributing factors, nonpharmacological treatment, such as exercise and psychosocial interventions, and pharmacologic approaches in managing CRF. Numerous drugs, such as psychostimulants (methylphenidate, dexamphetamines, modafi nil and pemoline), antidepressants, corticosteroids, L-carnitine, donepezil and guarana have been studied. Methylphenidate, modafi nil and guarana show the most promising results so far. However, additional randomized, placebo-controlled trials are needed to determine the benefi t of these and other drugs in the treatment of CRF.

Fatigue is one of the most distressing symptoms of cancer patients. Its characteristics and impact on quality of life have not been fully explored and treatment of cancer-related fatigue in Italian oncological centers has not been codified. A cross-sectional study was carried out on all patients attending for any reason the 24 participating centers in two non-consecutive days. Patients with fatigue filled out the Brief Fatigue Inventory (BFI) questionnaire and reported any pharmacological or non-pharmacological treatment for fatigue. From October 2014 to May 2015, 1394 cancer patients agreed to participate in the study. Fatigue was referred by 866 (62.1%) of patients; its duration was > 4months in 441 patients (50.9%). In the investigators' opinion, the most important (probable or almost sure) determinants of fatigue were reduced physical activity (271 patients), anxiety (149), pain (131), insomnia (125), anemia (123), and depression (123). Fatigue of moderate/severe intensity was reported by 43%/29.2% of patients, while usual fatigue in the last 24h by 45%/33.1%, and the worst fatigue in the last 24h by 33%/54.8%, respectively. Concerning the impact on quality of life, fatigue interfered moderately/severely with general activity in 30.8%/38.6% of patients, with mood in 26.1%/32.8%, with the ability to work in 27.9%/35.6%, with normal work in 26.7%/38.9%, with relationships with others in 21%/23.4% and with the ability to amuse themselves in 22.2%/33.1%. Only 117/866 patients (13.5%) received a pharmacological treatment represented by a corticosteroid in 101 patients (86.3%) while 188 patients (21.7%) received a non-pharmacological treatment such as physical exercise (120 patients, 63.8%) and various alimentary supplements (52 patients, 27.6%). Cancer-related fatigue is frequently reported by oncological patients; its intensity and impact on quality of life is relevant.

Objective: Cancer- related fatigue (CRF) is one of the most reported long-term effects after breast cancer and severely impacts quality of life. To come towards optimal treatment of multidimensional CRF, the first step is to use a holistic approach to develop a holistic patient profile including the patient’s experience and impact of CRF on their life. Methods and measures: Four semi- structured focus groups with twenty- seven breast cancer patients and fourteen interviews with healthcare professionals (HCPs) were held. Reflexive thematic analysis was used to define (sub)themes for the holistic patient profile. The themes of the interviews and focus groups were compared for validity. Results: Breast cancer patients and HCPs described the same five major themes, consisting of experience of CRF, impact and consequences, coping, personality, and CRF treatment. Experience of CRF consists of cognitive, emotional, and physical aspects. Impact and consequences include work, family, partner relation, social contact and hobbies, body, and misunderstanding. Coping consists of twelve (mal)adaptive strategies. Personality and CRF treatment were summarised as themes. Conclusions: A first holistic patient profile was introduced for CRF for breast cancer. This profile can be conceptualized into a questionnaire to collect information for personalized treatment recommendations and monitoring of CRF over time.

Objective: To systematically review the efficacy and safety of botanical drugs in the treatment of cancer-related fatigue (CRF) caused by gastric cancer (GC) and to determine the underlying pharmacological mechanisms using a network analysis. Methods: Databases such as China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) from inception to 18 April 2022. Methodological quality assessment was performed using the collaborative tool Cochrane, and data analysis were carried out using RevMan 5.4 and STATA 16 software. The botanical drugs with the highest frequency of use in the included studies was selected. The chemical composition, targets of action, disease targets, and shared targets of these botanical drugs were screened based on network analysis to explore the potential mechanisms of treating CRF in patients with gastric cancer (GC). Results: A total of 13 studies that included 986 patients with gastric CRF met the inclusion criteria. The results showed that botanical drugs could improve the CRF scores of gastric CRF, including the total scores of CRF dichotomous data [Odds Ratio (OR) = 4.22; 95% confidence interval (CI) 1.67–10.68; p = 0.002], the total scores of CRF continuous data [Standardized Mean Difference (SMD) = -0.98; 95% CI -1.36 to -0.60; p < 0.00001], the affective subscales of Piper Fatigue Scale (PFS) scores [Weighted Mean Difference (MD) = -0.79; 95%CI -0.92 to -0.65; p < 0.00001], the sensory subscales of PFS scores (MD = -0.57; 95%CI -0.77 to -0.37; p < 0.00001), the behavioral subscales of PFS scores (MD = -1.05; 95% CI -1.29 to -0.82; p < 0.00001), Quality of Life Questionnaire Core 30 (QLQ-C30) (MD = 10.53, 95% CI 8.26 to12.80; p < 0.00001), and the Karnofsky Performance Status scale (KPS) (MD = 5.18, 95% CI 2.60 to 7.76; p < 0.0001). The botanical drugs group had milder adverse effects than the control group. A total of 44 chemical components and 241 potential targets were obtained from the online database and 121 drug targets overlapped with the disease targets of CRF in patients with GC. Moreover, five key active ingredients, namely quercetin, Stigmasterol, luteolin, kaempferol, and isorhamnetin, as well as five key targets including AKT1, TP53, TNF, VEGFA, and CASP3, were screened. In addition, five key signaling pathways, including cancer, Hepatitis B, Prostate cancer, Hepatitis C, and Pancreatic cancer pathways, were obtained through enrichment analysis. Conclusion: The results of the study showed that botanical drugs have positive effects on CRF in patients with GC. However, more well-designed, multicenter, and large sample-sized Randomized Controlled Trials are required to evaluate the effectiveness of botanical drugs on CRF in patients with GC.

e23157 Background: Cancer-related fatigue (CRF) is a common symptom among patients with cancer. The efficacy of placebo, however, was never the main objective of any meta-analysis. Predicting the efficacy of placebo may facilitate researchers in designing future clinical trials for the treatment of CRF. Methods: We performed a systematic review searching for prospective clinical trials comparing any treatment versus placebo for the treatment of CRF. We included studies that enrolled patients with any primary site of neoplasia and any stage of cancer. We excluded all studies that assessed fatigue related to any treatment. The primary endpoint of this study is the mean effect of placebo on fatigue according to the Functional Assessment of Chronic Illness (FACIT-F) and Brief Fatigue Inventory (BFI) scales. The secondary endpoint was the proportion of patients who reported improvement in fatigue (response rate). Results: We found 520 studies, and 29 studies with 3,758 participants were included in the meta-analysis. Placebo had a mean effect of +4.88 (95%CI +2.45 to +7.29) using the FACIT-F scale, although it was statistically worse than the interventions studied (p = 0.005). Using the BFI scale, placebo had an average effect of +0.64 (95%CI +0.02 to +1.30), although it was also worse than the other interventions studied (p = 0.002). In terms of the response rate, 29% (95%CI 25%–32%) of patients taking a placebo reported a significant improvement in CRF compared to 36% of patients treated with other interventions (p = 0.030). Conclusions: Placebo treatments had a significant effect on CRF, and predicting these effects may help design future studies for CRF.

The clinical application and pharmacological mechanism of Bu-Zhong-Yi-Qi decoction for treating cancer-related fatigue: An overview

Background:Cancer-related fatigue (CRF), is a common distressing symptom of cancer. What's more, “Three anti-fatigue acupoints” is one of the most important components of “Jin's 3-needle therapy” created by Rui Jin, a professor of Guangzhou University of Chinese Medicine, which can be used in the treatment of CRF. In this article, researchers will assess the safety and effect of acupuncture at 3 anti-fatigue acupoints on CRF in patients with cancer.Methods:Literature search for relevant articles up to October 2018 will be carried out in 9 databases: Cochrane Library, Embase, PubMed, VIP, CBM, CNKI, Wanfang Database, CiNii, and OASIS. The included literatures will be randomized controlled trials of acupuncture at 3 anti-fatigue acupoints on CRF in patients with cancer. The certain common scales, which reflect the patients’ fatigue degree or life quality will be the primary outcome measures. The secondary outcome measures will be defined with the blood index. After collecting the data, we will utilize Stata V.13.0. to perform data synthesis, subgroup analysis, partial sequence analysis, sensitivity analysis, and so on. A funnel plot will be used to assess reporting biases. And the funnel plot will be evaluated by the Egger and Begg tests. The quality of evidence will be judged by the grading of recommendations assessment, development, and evaluation.Results:The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.Conclusion:Our study will provide the evidence for the clinical efficacy and safety of acupuncture at 3 anti-fatigue acupoints in the treatment of CRF.