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.
BACKGROUND: Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.
OBJECTIVES: To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.
SEARCH METHODS: For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.
DATA COLLECTION AND ANALYSIS: Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.
MAIN RESULTS: The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.
AUTHORS' CONCLUSIONS: There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
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.
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.
OBJECTIVES: The objectives of this systematic review were to: (1) identify supportive-care (psychosocial/behavioral, pharmacological, complementary or alternative) interventions that have been evaluated via randomized controlled trials (RCTs) to improve patient-reported health-related quality of life (HRQoL) among adults with brain tumors; (2) evaluate the quality of the intervention studies; and (3) evaluate if developed interventions have been efficacious at improving HRQoL, as compared to control conditions in RCTs.
METHODS: This systematic review was conducted using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Four databases were searched for RCTs of supportive-care interventions for adults with brain tumors, primary or metastatic, that included a patient-reported HRQoL outcome. Quality of the included studies was assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies.
RESULTS: Ten RCTs involving 640 patients with either a primary or metastatic brain tumor investigating supportive-care interventions with a HRQoL outcome were identified. In terms of quality, three of the studies received a "strong" rating, three received a "moderate" rating, and four of the studies received a "weak" rating. Only two of the interventions (i.e., a home-based psychosocial intervention and individualized acupuncture with standard rehabilitation) demonstrated improvements in HRQoL over control conditions.
CONCLUSIONS: HRQoL is of the utmost importance when treating patients with brain tumors. Yet, there is a notable paucity of research to inform clinical decisions and evidence-based practice. More high-quality studies of interventions aimed at improving HRQoL are needed.
BACKGROUND: Cognitive impairment is recognized as a common symptom experienced by cancer survivors which impacts on quality of life (QoL) and day-to-day activities. One of the treatment options is the use of psychostimulants but the evidence supporting its use remains unclear.
OBJECTIVES: To identify the level of evidence of psychostimulants' effect on the management of cognitive impairment in adult cancer survivors.
METHODS: Electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL) and reference lists of relevant reviews were searched from inception to December 2017, with no language restrictions applied. Randomized controlled trials (RCTs), evaluating the effect of psychostimulants on cognitive impairment among cancer patients with no primary or secondary brain tumor or brain radiation, were included. The primary outcome was cognitive function changes, whereas secondary outcomes were adverse events (AEs) and QoL.
RESULTS: Six RCTs were included: three studies investigating methylphenidate and three modafinil, with a total of 244 and 146 patients, respectively. Due to important differences in methodologies between studies, a meta-analysis was assumed inappropriate for the primary outcome. A narrative synthesis was performed. One study using methylphenidate and two using modafinil demonstrated improvements in some cognitive functions as measured by objective cognitive assessment tests. Psychostimulants did not improve QoL and were not associated with more AEs.
CONCLUSION: To date, limited evidence is available to estimate the usefulness (or lack) of psychostimulants on cognitive function in this population.
PURPOSE: Corticosteroids are commonly used in palliative care settings, but are associated with several side effects. Although adverse events (AEs) are highly distressing for patients, few data are available from prospective studies to look at incidence or predictors of such harms. The aim of this study is to identify AE reporting among studies of patients with advanced cancer receiving corticosteroids for any reason.
METHODS: A systematic review was conducted using the following data sources: PubMed, Medline, SCOPUS, Cochrane reviews, and CINAHL. Randomized controlled trials (RCTs) with patients with advanced cancer assessing the effect of corticosteroids were included. Consecutive cohort observational studies of corticosteroid toxicities in cancer patients were also included.
RESULTS: Twenty-seven RCTs and 12 consecutive cohort observational studies were identified. The most frequently reported primary outcome of RCTs was nausea and vomiting (8/27). Dexamethasone was prescribed in almost half of RCTs (13/27). In consecutive cohort studies, the primary outcomes were a wide variety of symptoms. Dexamethasone was also the most common glucocorticoid used (7/12). In terms of quality of AE reporting, two RCTs and one consecutive cohort study used a validated AE assessment tool in their studies.
CONCLUSIONS: Side effects of corticosteroids in advanced cancer patients were poorly reported with few data using validated tools. Researchers should be aware of the guideline of AE reporting to provide the best evidence of risk-benefit balance. Developing specific consensus guidelines about AE reporting in studies of glucocorticoids in studies of people with advanced cancer would be useful.
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.
PURPOSE OF REVIEW: To review recent evidence on the efficacy and safety of methylphenidate as a symptomatic treatment of patients with cancer-related fatigue (CRF).
RECENT FINDINGS: Five clinical trials published since 2011 were identified. Two of these concluded that methylphenidate is more efficacious than placebo in providing relief from CRF, but the remaining three showed no difference in favour of methylphenidate. The studies were heterogeneous as per the dosage, scales used for evaluating fatigue and the target group studied. None of the studies detected serious reactions, and only mild and infrequent side-effects of methylphenidate were reported. Three new metanalyses show the slightly superior effect of methylphenidate compared to placebo in CRF.
SUMMARY: Overall, literature supports the existence of moderate benefit of methylphenidate in CRF, backed up by weak evidence. Future studies should aim at better identifying the profile of patients who would benefit most from this pharmacological intervention.
Background: Carnitine deficiency has been implicated as a potential pathway for cancer-related fatigue that could be treated with carnitine supplementation. The aim of this systematic literature review and meta-analysis was to evaluate the literature regarding the use of supplemental carnitine as a treatment for cancer-related fatigue. Methods: Using the PRISMA guidelines, an electronic search of the Cochrane Library, MEDLINE, Embase, CINAHL and reference lists was conducted. Data were extracted and independently assessed for quality using the Academy of Nutrition and Dietetics evidence analysis by two reviewers. In studies with positive quality ratings, a meta-analysis was performed using the random-effects model on Carnitine and cancer-related fatigue. Results: Twelve studies were included for review with eight reporting improvement in measures of fatigue, while four reported no benefit. However, many studies were non-randomized, open-label and/or used inappropriate dose or comparators. Meta-analysis was performed in three studies with sufficient data. Carnitine did not significantly reduce cancer-related fatigue with a standardized mean difference (SMD) of 0.06 points ((95% CI −0.09, 0.21); p = 0.45). Conclusion: Results from studies with lower risk of bias do not support the use of carnitine supplementation for cancer-related fatigue.
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.
