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Systematic review

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Efficacy and safety of methylphenidate and ginseng in cancer-related fatigue: a network meta-analysis of randomized controlled trials

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Authors Li H , Che K , Zhi Z , Xu W , Huang J , Wang X , Liang X , Zhao T , Hu J , Hou T , Sun S , He J
Journal Translational cancer research
Year 2023
Links Pubmed DOI PubMed Central

This article includes 14 Primary studies 13 Primary studies (14 references)

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BACKGROUND: Incidence of cancer-related fatigue (CRF), which can persist 5 to 10 years, is nearly 85% in cancer patients. It severely affects the quality of life and is strongly associated with poor prognosis. As clinical trial data on CRF treated with methylphenidate and ginseng, two potential medicines, has been accumulating, an updated meta-analysis was performed to evaluate and compare the efficacy and safety of the two medicines in CRF. METHODS: Randomized controlled trials that investigated methylphenidate or ginseng in the treatment of CRF were identified through a literature search. The primary outcome was CRF relief. Standardized mean difference (SMD) was used to analyze the effect. RESULTS: Eight studies on methylphenidate were included and the pooled SMD was 0.18 [95% confidence interval (95% CI): -0.00 to 0.35, P=0.05]. Five studies on ginseng were included and the SMD was 0.32 (95% CI: 0.17-0.46, P<0.0001). Results of network meta-analysis showed that the order was ginseng, methylphenidate, placebo from high efficacy to low and ginseng was significantly better than methylphenidate (SMD =0.23, 95% CI: 0.01-0.45). Incidences of insomnia and nausea caused by ginseng were significantly lower than those caused by methylphenidate (P<0.05). CONCLUSIONS: Both methylphenidate and ginseng can significantly ameliorate CRF. Ginseng may be superior to methylphenidate because ginseng may be more effective and might cause less adverse events. Head-to-head trials with fixed protocol are warranted to identify the optimal medical strategy.

Systematic review

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Effect of post-diagnosis exercise on depression symptoms, physical functioning and mortality in breast cancer survivors: A systematic review and meta-analysis of randomized control trials.

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Journal Cancer epidemiology
Year 2022
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This article includes 26 Primary studies 26 Primary studies (26 references)

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BACKGROUND: Cancer is the second leading cause of death worldwide. Breast cancer, the most common cancer found in women, affects 2.1 million women annually and has the highest number of cancer related deaths. The objective of the current meta-analysis is to evaluate the effects of post-diagnosis exercises on depression, physical functioning, and mortality in breast cancer survivors. METHODS: The search for eligible articles was conducted through CINAHL, Medline/PubMed, Scopus, Cochrane, Emerald Insight and Web of Science, Embase database, MEDLINE In-Process, Elsevier, Google Scholar, PsycInfo, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Allied and Complementary Medicine (AMED), Biosis Previews, SPORTDiscus, PEDro scientific databases from 1974 to 2020. Following the exclusion procedure, 26 articles yielded for final analysis. The combined statistics for depression, physical functioning, and mortality in breast cancer survivors were calculated using standardized mean differences (SMD). Standard errors and 95% confidence intervals (CI) were converted to standard deviations as required. For mortality, combined statistics were calculated using hazard ratios (HR). The 95% CIs were converted to standard errors as required. The forest plots display point estimates and 95% CIs. RESULTS: Statistically significant improvements on levels of depression were identified following the exercise intervention, suggesting that post-diagnosis physical activity leads to a decrease in depression scores. Overall, post-diagnosis exercise led to a 37% reduction in the rate of breast cancer-specific mortality. The all-cause mortality rate was decreased by 39% with the inclusion of moderate physical activity as the part of daily routine. CONCLUSIONS: Future studies should look at how to improve the quality of life while incorporating physical activity as a daily routine after breast-cancer treatment.

Systematic review

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Effects of yoga on improving quality of life in patients with breast cancer: a meta-analysis of randomized controlled trials.

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Authors Hsueh EJ , Loh EW , Lin JJ , Tam KW
Journal Breast cancer (Tokyo, Japan)
Year 2021
Links Pubmed DOI

This article includes 26 Primary studies 26 Primary studies (26 references)

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BACKGROUND: Complications of breast cancer treatment can cause physical and psychosocial distress in patients. Yoga demonstrates substantial potential as a supportive therapy for patients with breast cancer. Our aim is to conduct a meta-analysis of randomized controlled trials to evaluate the effectiveness of yoga in enhancing the quality of life (QoL) of patients with breast cancer. METHODS: We searched for studies published before March 2020 in the PubMed, Embase, and Cochrane Library databases. Individual effect sizes were standardized, and the pooled effect size was calculated using a random effect model. Measured outcomes included QoL, anxiety and depression, stress, fatigue, pain severity, and sleep quality. RESULTS: In total, 26 trials involving 2069 patients were reviewed. Significant enhancement in QoL was observed immediately after the yoga intervention. The pooled mean differences in social (weighted mean difference [WMD]: 1.36, 95% confidence interval [CI] 0.12-2.61), emotional (WMD: 1.46, 95% CI 0.26-2.66), and functional well-being (WMD: 2.04, 95% CI 0.21-3.87) were significantly higher in the yoga group than in the control group. Patients practicing yoga exhibited significant improvements in physical well-being, mental well-being, and sleep quality as well as reductions in anxiety, depression, stress, fatigue, and pain severity after the intervention. CONCLUSIONS: Yoga may enhance QoL in patients with breast cancer experiencing post-treatment complications. Therefore, we recommend yoga as a supportive therapy for patients with breast cancer to relieve post-treatment distress.

Systematic review

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Massage Therapy for Fatigue Management in Breast Cancer Survivors: A Systematic Review and Descriptive Analysis of Randomized Controlled Trials

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Authors Wang T , Zhai J , Liu XL , Yao LQ , Tan JB
Journal Evidence-based complementary and alternative medicine : eCAM
Year 2021
Links Pubmed DOI PubMed Central

This article includes 10 Primary studies 10 Primary studies (10 references)

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BACKGROUND: Fatigue is one of the most common symptoms among breast cancer survivors. Although massage therapy has been commonly used for fatigue management, relevant evidence on the effectiveness of massage therapy for the reduction of fatigue in breast cancer survivors is still unclear. OBJECTIVE: To identify the research evidence on the effectiveness and safety of massage therapy to manage fatigue in breast cancer survivors and summarize the characteristics of massage therapy protocols utilized for fatigue management in breast cancer survivors. METHODS: Randomized controlled trials (RCTs) using massage therapy to manage cancer-related fatigue were searched in PubMed, Medline, Web of Science, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ScienceDirect, PsycINFO, Wan Fang Data, and China National Knowledge Infrastructure (CNKI) from the inception of each database to March 2021. The Cochrane Back Review Group Risk of Bias Assessment Criteria was used to assess the methodological quality of the included studies. Descriptive analysis was applied for a summary and synthesis of the findings. The primary outcome was fatigue measured by any patient-reported questionnaires, and the secondary outcomes were quality of life and massage-therapy-related adverse events. RESULTS: Ten RCTs were included. Massage therapy was found to have a positive effect on fatigue management compared with routine care/wait list control groups and sham massage. Despite these encouraging findings, the review concluded that most of the included studies exhibited an unsatisfactory experimental design, particularly, inadequate blinding and allocation concealment. The duration and frequency of the massage therapy interventions varied across the studies. Adverse events were reported in three included studies, with no study conducting causality analysis. CONCLUSION: This systematic review provides the latest research evidence to support massage therapy as an encouraging complementary and alternative medicine approach to managing fatigue in breast cancer survivors. More rigorously designed, large-scale, sham-controlled RCTs are needed to further conclude the specific therapeutic effectiveness and safety issues of massage therapy for fatigue management.

Systematic review

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Acupuncture for Breast Cancer: A Systematic Review and Meta-Analysis of Patient-Reported Outcomes

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Authors Zhang Y , Sun Y , Li D , Liu X , Fang C , Yang C , Luo T , Lu H , Li H , Zhang H , Liang Q , Wu J , Huang L , Xu R , Ren L , Chen Q
Journal Frontiers in oncology
Year 2021
Links Pubmed DOI PubMed Central

This article includes 33 Primary studies 33 Primary studies (33 references)

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Abstract: The present systematic review and meta-analysis was undertaken to evaluate the effects of acupuncture in women with breast cancer (BC), focusing on patient-reported outcomes (PROs). Methods: A comprehensive literature search was carried out for randomized controlled trials (RCTs) reporting PROs in BC patients with treatment-related symptoms after undergoing acupuncture for at least four weeks. Literature screening, data extraction, and risk bias assessment were independently carried out by two researchers. Results: Out of the 2, 524 identified studies, 29 studies representing 33 articles were included in this meta-analysis. At the end of treatment (EOT), the acupuncture patients’ quality of life (QoL) was measured by the QLQ-C30 QoL subscale, the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), the Functional Assessment of Cancer Therapy–General/Breast (FACT-G/B), and the Menopause-Specific Quality of Life Questionnaire (MENQOL), which depicted a significant improvement. The use of acupuncture in BC patients lead to a considerable reduction in the scores of all subscales of the Brief Pain Inventory-Short Form (BPI-SF) and Visual Analog Scale (VAS) measuring pain. Moreover, patients treated with acupuncture were more likely to experience improvements in hot flashes scores, fatigue, sleep disturbance, and anxiety compared to those in the control group, while the improvements in depression were comparable across both groups. Long-term follow-up results were similar to the EOT results. Conclusions: Current evidence suggests that acupuncture might improve BC treatment-related symptoms measured with PROs including QoL, pain, fatigue, hot flashes, sleep disturbance and anxiety. However, a number of included studies report limited amounts of certain subgroup settings, thus more rigorous, well-designed and larger RCTs are needed to confirm our results.

Systematic review

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Pharmacological Interventions for the Management of Cancer-Related Fatigue Among Cancer Survivors: Systematic Review and Meta-Analysis.

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Authors Sun X , Chen Y , Cheung WK , Wu IX , Xiao F , Chung VC
Journal Integrative cancer therapies
Year 2021
Links Pubmed DOI PubMed Central

This article includes 15 Primary studies 15 Primary studies (15 references)

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OBJECTIVE: Current guidelines have different recommendations on applying pharmacological interventions for managing cancer-related fatigue (CRF) among cancer survivors. This systematic review aims to synthesize clinical evidence on pharmacological interventions for managing CRF. METHODS: Five databases were searched for potential randomized controlled trials (RCTs) from their inception until October 2020. RCTs assessing the effect of pharmacological treatments for CRF among cancer survivors were considered eligible. Clinical significance was determined by comparing the estimated effect with that of minimal important difference (MID). The risk of bias of each included RCT was appraised using the Cochrane risk of bias tool for randomized trials 2. Data were synthesized using random-effect pairwise meta-analyses. RESULTS: A total of 15 RCTs (1238 participants) were included. The majority presented some concerns of bias arising from the randomization process and selection of the reported results. Meta-analysis showed that psychostimulant and wakefulness agents had statistically significant while clinically insignificant effects on the treatment of CRF (pooled weighted mean difference [WMD]: 2.8, 95% confidence interval [CI]: 0.2-5.4, I2: 0%, 3 RCTs, MID: 3.0-6.0). Three natural products, including Renshen Yangrong Tang (mean difference [MD]: -16.1, 95% CI: -8.9 to -23.3, MID: -17.3 to -11.4), Tualang honey (MD: 11.2, 95% CI: 7.1-15.3, MID: 3.0-6.0), and Shenmai injection plus Peptisorb (MD: -1.6, 95% CI: -2.1 to -1.1, MID: -1.1 to -0.8) demonstrated statistically and clinically significant effect in reducing CRF. CONCLUSIONS: Existing evidence showed promising effects of 3 natural products in reducing CRF among cancer survivors. The results from this study need to be further confirmed with well-designed and adequately powered RCTs that use validated instruments for the measurement of CRF.

Systematic review

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The efficacy of placebo for the treatment of cancer-related fatigue: a systematic review and meta-analysis.

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Journal Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Year 2020
Links Pubmed DOI

This article includes 29 Primary studies 28 Primary studies (29 references)

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PURPOSE: 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 3758 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 with 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.

Systematic review

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Placebo response in trials of drug treatments for cancer-related fatigue: A systematic review, meta-analysis and meta-regression

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Authors Roji R , Stone P , Ricciardi F , Candy B
Journal BMJ supportive & palliative care
Year 2020
Links Pubmed DOI PubMed Central Pubmed central

This article includes 30 Primary studies 30 Primary studies (30 references)

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Background Cancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors. Method RCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool. Results From 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was -0.23 (95% confidence intervals -0.42 to -0.04). None of the variables analysed in the meta-regression were statistically significant related to PR. Conclusion There is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results. ©

Systematic review

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Effects of exercise on the quality of life in breast cancer patients: a systematic review of randomized controlled trials

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Authors Zhang X , Li Y , Liu D
Journal Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Year 2019
Links Pubmed DOI

This article includes 36 Primary studies 36 Primary studies (36 references)

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Purpose: The purpose of this study was to conduct a systematic review to assess the effect of exercise on the quality of life among people with breast cancer. Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Library, PubMed, EMBASE, Web of Science, CINAHL, and four Chinese databases were searched for studies published until January 2018. The review included all randomized controlled trials that evaluated the effect of exercise on quality of life compared with that of usual care for people with breast cancer. Two reviewers independently assessed the quality of all the included studies using the Cochrane Handbook for Systematic Reviews of Interventions. Results: In total, 36 studies (3914 participants) met the inclusion criteria. We divided the exercise into three modes: aerobic, resistance, and a combination of aerobic and resistance. All three modes of exercise intervention showed a significant effect on quality of life between groups. Conclusions: Exercise is a safe and effective method of improving the quality of life in patients with breast cancer. In particular, combined training was associated with a significant improvement in quality of life. In future research, more high-quality, multicenter trials evaluating the effect of exercise in breast cancer patients are needed. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Systematic review

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Pharmacologic interventions for fatigue in cancer and transplantation: a meta-analysis.

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Journal Current oncology (Toronto, Ont.)
Year 2018
Links Pubmed DOI PubMed Central

This article includes 117 Primary studies 116 Primary studies (117 references)

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BACKGROUND: Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (hsct). METHODS: For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, cinahl, and Psychinfo for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of hsct. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models. RESULTS: In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins ( CONCLUSIONS: Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of hsct. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.