A Double-Blind, Randomized, Placebo-Controlled Trial of Panax Ginseng for Cancer-Related Fatigue in Patients With Advanced Cancer. Rayyan—a web and mobile app for systematic reviews Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial Effects of infrared laser moxibustion on cancer‐related fatigue: A randomized, double‐blind, placebo‐controlled trial A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial. The Effect of Acupuncture on Post-Cancer Fatigue and Well-Being for Women Recovering from Breast Cancer: A Pilot Randomised Controlled Trial Effectiveness of guaraná (Paullinia cupana) for postradiation fatigue and depression: results of a pilot double-blind randomized study. A phase 3 trial of armodafinil for the treatment of cancer-related fatigue for patients with multiple myeloma Phase II, randomised, double‐blind, placebo‐controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH‐agonist therapy A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. Guarana (Paullinia cupana) improves fatigue in breast cancer patients undergoing systemic chemotherapy. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. Donepezil for cancer fatigue: a double-blind, randomized, placebo-controlled trial. Pilot, randomized, modified, double-blind, placebo-controlled trial of acupuncture for cancer-related fatigue. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer. Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: a placebo-controlled double-blind randomised trial. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial. Effects of infrared laser moxibustion on cancer-related fatigue in breast cancer survivors Open-Label Placebo Treatment for Cancer-Related Fatigue: A Randomized-Controlled Clinical Trial
Background : Despite the high frequency , severity , and effects of cancer-related fatigue ( CRF ) on the quality of life ( QoL ) of patients with cancer , limited treatment options are available . The primary objective of this study was to compare the effects of oral Panax ginseng extract ( PG ) and placebo on CRF . Secondary objectives were to determine the effects of PG on QoL , mood , and function . Methods : In this r and omized , double-blind , placebo-controlled study , patients with CRF ≥4/10 on the Edmonton Symptom Assessment System ( ESAS ) were eligible . Based on a pilot study , we r and omized patients to receive either 400 mg of st and ardized PG twice daily or a matching placebo for 28 days . The primary end point was change in the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) subscale from baseline to day 29 . Results : Of 127 patients , 112 ( 88.2 % ) were evaluable . The mean ( SD ) FACIT-F subscale scores at baseline , day 15 , and day 29 were 22.4 ( 10.1 ) , 29.9 ( 10.6 ) , and 30.1 ( 11.6 ) for PG ( P<.001 ) , and 24.0 ( 9.4 ) , 30.0 ( 10.1 ) , and 30.4 ( 11.5 ) for placebo ( P<.001 ) . Mean ( SD ) improvement in the FACIT-F subscale at day 29 was not significantly different in the PG than in the placebo group ( 7.5 [ 12.7 ] vs 6.5 [ 9.9 ] ; P=.67 ) . QoL , anxiety , depression , symptoms , and functional scores were not significantly different between the PG and placebo groups . Improvement in the FACIT-F subscale correlated with baseline scores ( P=.0005 ) , Hospital Anxiety and Depression Scale results ( P=.032 ) , and sex ( P=.023 ) . There were fewer any- grade toxicities in the PG versus placebo group ( 28/63 vs 33/64 ; P=.024 ) . Conclusions : Both PG and placebo result in significant improvement in CRF . PG was not significantly superior to placebo after 4 weeks of treatment . There is no justification to recommend the use of PG for CRF . Further studies are needed . Trial Registration : Clinical Trials.gov identifier : NCT01375114 Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment . Dexmethylpheni date ( D-MPH ; the D-isomer of methylpheni date ) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment . A r and omized , double-blind , placebo-controlled , parallel-group study evaluated the potential therapeutic effect and safety of D-MPH in the treatment of patients with chemotherapy-related fatigue . Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale ( FACIT-F ) total score at Week 8 was the primary outcome measure . One hundred fifty-four patients ( predominantly with breast and ovarian cancers ) were r and omized and treated . Compared with placebo , D-MPH-treated subjects demonstrated a significant improvement in fatigue symptoms at Week 8 in the FACIT-F ( P=0.02 ) and the Clinical Global Impression-Severity scores ( P=0.02 ) , without clinical ly relevant changes in hemoglobin levels . Cognitive function was not significantly improved . There was a higher rate of study drug-related adverse events ( AEs ) ( 48 of 76 [ 63 % ] vs. 22 of 78 [ 28 % ] ) and a higher discontinuation rate because of AEs ( 8 of 76 [ 11 % ] vs. 1 of 78 [ 1.3 % ] ) in D-MPH-treated subjects compared with placebo-treated subjects . The most commonly reported AEs independent of study drug relationship in D-MPH-treated subjects were headache , nausea , and dry mouth , and in placebo-treated subjects were headache , diarrhea , and insomnia .  D-MPH produced significant improvement in fatigue in subjects previously treated with cytotoxic chemotherapy . Further studies with D-MPH or other agents to explore treatment response in chemotherapy-associated fatigue should be considered Background Uncontrolled studies show fatigue , anorexia , depression , and mortality are associated with low testosterone in men with cancer .  Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions . The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer , by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale ( FACIT-Fatigue ) at day 29 . Methods This is a r and omized , double-blinded placebo-controlled trial . Out patients with advanced cancer , bioavailable testosterone ( BT ) < 70 ng/dL and fatigue score > 3/10 on the Edmonton Symptom Assessment Scale were eligible .  Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70–270 ng/dL. Results Sixteen placebo and 13 testosterone-treated subjects were evaluable . No statistically significant difference was found for FACIT-fatigue scores between arms ( −2 ± 12 for placebo , 4 ± 8 for testosterone , p = 0.11 ) . Sexual Desire Inventory score ( p = 0.054 ) and performance status ( p = 0.02 ) improved in the testosterone group . Fatigue subscale scores were significantly better ( p = 0.03 ) in those treated with testosterone by day 72 . Conclusions Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life . Larger studies of longer duration are warranted Fatigue is the most common symptom negatively affecting the quality of life of patients with cancer . The objective of the current study was to evaluate the preliminary efficacy and safety of 10.6‐μm infrared laser moxibustion for cancer‐related fatigue ( CRF ) PURPOSE This study investigated the efficacy of the botanical-derived drug , PG2 , a partially purified extract of Astragalus membranaceus , as a complementary and palliative medicine for managing  cancer-related fatigue ( CRF ) .  METHODS Patients with advanced cancer and moderate to severe CRF were r and omized to receive either PG2 or a placebo ( normal saline , NS ) in the first treatment cycle ( four weeks ) in a double-blind manner ; thereafter , on the next cycle ( four weeks ) , all patients received open-label treatment with PG2 . RESULTS PG2 significantly improved CRF in the NS-primed group . In the first four week cycle , PG2 administration result ed in a greater fatigue-improvement response rate than seen with NS alone . In addition , approximately 82 % of patients who reported an improvement of fatigue symptoms following the first cycle of PG2 experienced sustained benefits after administration of the second treatment cycle . Among patients treated with PG2 who did not report an improvement in symptoms throughout the first treatment cycle , approximately 71 % showed significant improvement after the second treatment cycle . No major or irreversible toxicities were observed with PG2 treatment . CONCLUSION PG2 might be an effective and safe treatment for relieving CRF among advanced cancer patients PURPOSE Fatigue is a distressing symptom occurring in more than 60 % of patients with cancer . The CNS stimulants modafinil and methylpheni date are recommended for the treatment of cancer-related fatigue , despite a limited evidence base . We aim ed to evaluate the efficacy and tolerability of modafinil in the management of fatigue in patients with non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Adults with advanced NSCLC and performance status of 0 to 2 , who were not treated with chemotherapy or radiotherapy within the last 4 weeks , were r and omly assigned to daily modafinil ( 100 mg on days 1 to 14 ; 200 mg on days 15 to 28 ) or matched placebo . The primary outcome was change in Functional Assessment of Chronic Illness Therapy ( FACIT ) -Fatigue score from baseline to 28 days , adjusted for baseline fatigue and performance status . Secondary outcomes included safety and patient-reported measures of depression , daytime sleepiness , and quality of life . RESULTS A total of 208 patients were r and omly assigned , and 160 patients ( modafinil , n = 75 ; placebo , n = 85 ) completed question naires at both baseline and day 28 and were included in the modified intention-to-treat analysis . FACIT-Fatigue scores improved from baseline to day 28 ( mean score change : modafinil , 5.29 ; 95 % CI , 2.57 to 8.02 ; placebo , 5.09 ; 95 % CI , 2.54 to 7.65 ) , but there was no difference between treatments ( 0.20 ; 95 % CI , -3.56 to 3.97 ) . There was also no difference between treatments for the secondary outcomes ; 47 % of the modafinil group and 23 % of the placebo group stated that the intervention was not helpful . CONCLUSION Modafinil had no effect on cancer-related fatigue and should not be prescribed outside a clinical trial setting . Its use was associated with a clinical ly significant placebo effect Objective To determine the feasibility and acceptability of acupuncture in managing fatigue and well-being in breast cancer survivors . Methods A r and omised controlled trial compared acupuncture was with sham acupuncture and wait list controls was performed in Sydney , Australia . A total of 30 women with fatigue following breast cancer treatment participated in the trial . Women received six sessions of acupuncture over 8 weeks . Outcomes related to an assessment of interest to participate in the trial and identification of appropriate recruitment strategies , appropriateness of eligibility criteria and compliance with treatment attendance . Clinical outcomes assessed fatigue and well-being . In-depth interviews were undertaken with seven women , who described their experience of acupuncture . Results Our study demonstrated feasibility with appropriate trial entry criteria , good acceptability and treatment compliance with the study interventions , and with the completion of outcome forms . There was a significant reduction in fatigue for women receiving acupuncture compared with control after 2 weeks mean difference ( MD ) 5.3 , 95 % CI 4.5 to 6.2 , p=0.05 , and a significant improvement in well-being at 6 weeks for acupuncture compared with the sham and wait list control , MD 2.7 , 95 % CI 2.1 to 3.2 , p=0.006 . Women described their experience of acupuncture positively , and interview data may also offer explanations for the improved outcomes of well-being , with women reporting an improvement in sleep , mood and relaxation . Conclusions Fatigue is a common symptom experienced by people recovering from treatment , and an appropriately powered trial to evaluate the effect of acupuncture is needed . Clinical Trial Registration Australian New Zeal and Clinical Trials Registry , www.anzctr.org.au ACTRN12610000720011 CONTEXT AND OBJECTIVE Guaraná ( Paullinia cupana ) has been used medicinally for centuries . The aim of this study is evaluate the effectiveness of guaraná in the treatment of postradiation depression and fatigue . DESIGN AND SETTING This study had a double-blind r and omized design with crossover between experimental arms , at Faculdade de Medicina da Fundação do ABC . METHODS We conducted a r and omized double-blind crossover trial with 36 patients with breast cancer undergoing adjuvant radiation therapy . We r and omized patients to either guaraná 75 mg daily p.o . or to placebo . Patients were switched to the other experimental arm at the middle of the radiation treatment , which consisted of 28 daily fractions of 180 cGy . Evaluations were conducted at the beginning , at the middle , and at the end of radiation therapy . RESULTS We were unable to show any statistically significant differences between the guaraná and the placebo-treated group with any of the measured scores . Also , within the same group , we did not see any statistically significant associations during either the guaraná- or placebo-treated periods with any of the aforementioned measures . CONCLUSIONS We were unable to show that patients with breast cancer undergoing radiation therapy derive any advantage with guaraná over placebo for both fatigue and depressive symptoms Purpose Fatigue is a common problem among multiple myeloma ( MM ) patients .  Armodafinil is a drug known to promote wakefulness , which is related to modafinil , a compound that improves fatigue in some cancer patients treated with chemotherapeutic agents . We investigated whether armodafinil could reduce cancer-related fatigue in MM patients . Methods This double-blind , placebo-controlled phase 3 trial evaluated the efficacy of armodafinil in MM patients with evidence of moderate fatigue . Patients were r and omized to one of two arms : treatment-only ,  with armodafinil given at 150 mg/daily for 56 days , or placebo-first , with placebo given on days 1–28 , followed by armodafinil administered at 150 mg daily on days 29–56 . Fatigue was measured on days 1 ( pre-dose : baseline ) , 15 , 28 , 43 , and 56 using seven separate assessment s , including four patient-reported outcomes of fatigue and related quality of life measures , as well as three objective measures of cognitive function . Results Overall toxicities were similar between treatment groups . No significant differences were observed between the placebo-first and the treatment-only arms after 28 days . Treatment with armodafinil for 28 additional days did not produce responses . Both placebo-first and treatment-only patients showed similar significant improvements in three patient-reported measures and one objective task at day 28 compared to baseline . Placebo-first patients improved on eight additional measures ( one patient-reported measure , six subscales , and one objective task ) , suggesting a strong placebo effect in this patient population . Conclusions Evaluation and treatment of cancer-related fatigue continues to be challenging ; a clear definition of this symptom and better assessment tools are needed To investigate whether methylpheni date can alleviate fatigue , as measured by the Functional Assessment of Cancer Therapy : Fatigue subscale , in men with prostate cancer ( PCa ) treated with a luteinizing hormone‐releasing hormone ( LHRH ) for a minimum of 6 months , and to assess changes in global fatigue and quality of life ( QoL ) as measured by the Bruera Global Fatigue Severity Scale ( BFS ) and the Medical Outcomes Study 36‐Item Short‐Form Health Survey ( SF‐36 ) , respectively Background Women who receive adjuvant chemotherapy for breast cancer develop fatigue , and a subset reports cognitive impairment . Methylpheni date is reported to improve fatigue and to decrease cognitive impairment in other population s. Material s and methods Women were r and omised early during their chemotherapy  to receive d-methylpheni date ( d-MPH ) , a form of methylpheni date , or an identical appearing placebo . All participants took placebo for one cycle to ensure compliance and then study medication until completion of chemotherapy . Subjects were assessed at baseline , end of chemotherapy and at ∼6 months follow-up with the High Sensitivity Cognitive Screen ( HSCS ) and the Hopkins Verbal Learning Test-Revised ( HVLT-R ) . They also completed the self-report Functional Assessment of Cancer Therapy-General ( FACT-G ) and FACT-F ( F = fatigue ) question naires , evaluating quality of life and fatigue . Results A total of 57 evaluable women were r and omised : 29 to d-MPH and 28 to placebo ; the study did not meet its accrual goal of 170 patients , mainly because women were reluctant to take additional medication in general and methylpheni date in particular . Groups were well matched for age ( median , 50 years ) and education . d-MPH and placebo were well tolerated . There were no significant differences between the r and omised groups in classification of cognitive function by HSCS or in summed FACT-F fatigue scores ( the primary endpoints of the study ) at any of the assessment s. There were also no differences in HLTV-R scores or quality of life . Conclusions This study is underpowered , but there are no trends to suggest that d-MPH , taken concurrently with adjuvant chemotherapy , improves quality of life or fatigue ABSTRACT Objective To investigate the effects of oral zinc supplementation on fatigue intensity and quality of life of patients during chemotherapy for colorectal cancer . Methods A prospect i ve , r and omized , double-blinded , placebo-controlled study was conducted with 24 patients on chemotherapy for colorectal adenocarcinoma in a tertiary care public hospital . The study patients received zinc capsules 35 mg ( Zinc Group , n=10 ) or placebo ( Placebo Group , n=14 ) orally , twice daily ( 70mg/day ) , for 16 weeks , from the immediate postoperative period to the fourth chemotherapy cycle . Approximately 45 days after surgical resection of the tumor , all patients received a chemotherapeutic regimen . Before each of the four cycles of chemotherapy , the Functional Assessment of Chronic Illness Therapy-Fatigue scale was completed . We used a linear mixed model for longitudinal data for statistical analysis . Results The scores of quality of life and fatigue question naires were similar between the groups during the chemotherapy cycles . The Placebo Group presented worsening of quality of life and increased fatigue between the first and fourth cycles of chemotherapy , but there were no changes in the scores of quality of life or fatigue in the Zinc Group . Conclusion Zinc supplementation prevented fatigue and maintained quality of life of patients with colorectal cancer on chemotherapy Purpose This pilot trial sought to investigate whether any of three doses of American ginseng ( Panax quinquefolius ) might help cancer-related fatigue . A secondary aim was to evaluate toxicity . Methods Eligible adults with cancer were r and omized in a double-blind manner , to receive American ginseng in doses of 750 , 1,000 , or 2,000 mg/day or placebo given in twice daily dosing over 8 weeks . Outcome measures included the Brief Fatigue Inventory , vitality subscale of the Medical Outcome Scale Short Form-36 ( SF-36 ) , and the Global Impression of Benefit Scale at 4 and 8 weeks . Results Two hundred ninety patients were accrued to this trial . Nonsignificant trends for all outcomes were seen in favor of the 1,000- and 2,000-mg/day doses of American ginseng . Area under the curve analysis of activity interference from the Brief Fatigue Inventory was 460–467 in the placebo group and 750 mg/day group versus 480–551 in the 1,000- and 2,000-mg/day arms , respectively . Change from baseline in the vitality subscale of the SF-36 was 7.3–7.8 in the placebo and the 750-mg/day arm , versus 10.5–14.6 in the 1,000- and 2,000-mg/day arms . Over twice as many patients on ginseng perceived a benefit and were satisfied with treatment over those on placebo . There were no significant differences in any measured toxicities between any of the arms . Conclusion There appears to be some activity and tolerable toxicity at 1,000–2,000 mg/day doses of American ginseng with regard to cancer-related fatigue . Thus , further study of American ginseng is warranted PURPOSE L-carnitine , a popular complementary and alternative medicine product , is used by patients with cancer for the treatment of fatigue , the most commonly reported symptom in this patient population . The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer . PATIENTS AND METHODS In this double-blind , placebo-controlled trial , patients with invasive malignancies and fatigue were r and omly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo . The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory ( BFI ) . RESULTS Three hundred seventy-six patients were r and omly assigned to treatment with L-carnitine supplementation or placebo . L-carnitine supplementation result ed in significant carnitine plasma level increase by week 4 . The primary outcome , fatigue , measured using the BFI , improved in both arms compared with baseline ( L-carnitine : -0.96 , 95 % CI , -1.32 to -0.60 ; placebo : -1.11 , 95 % CI -1.44 to -0.78 ) . There were no statistically significant differences between arms ( P = .57 ) . Secondary outcomes , including fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue instrument , depression , and pain , did not show significant difference between arms . A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation . CONCLUSION Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status BACKGROUND In patients with breast cancer ( BC ) undergoing systemic chemotherapy , cancer-related fatigue ( CRF ) is a common problem that can negatively impact quality of life . Guarana ( Paullinia cupana ) is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times . OBJECTIVE The purpose of this study was to evaluate the effectiveness of guarana extract on fatigue , sleep quality , anxiety , depression symptoms , and menopause in a group of BC chemotherapy patients . PATIENTS AND METHODS Patients with progressive fatigue after their first cycle of chemotherapy were r and omized to receive either guarana 50 mg by mouth twice daily ( 32 patients ) or placebo ( 43 patients ) for 21 days . After a 7-day washout period , patients were crossed over to the opposite experimental arm . All patients were evaluated on days 1 , 21 , and 49 . The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) question naire score , and secondary endpoints were the results of the Functional Assessment of Chronic Illness Therapy-Endocrine Symptoms ( FACT-ES ) , Brief Fatigue Inventory ( BFI ) , Pittsburg Sleep Quality Index , Chalder Fatigue Scale , and Hospital Anxiety and Depression Scale . RESULTS Guarana significantly improved the FACIT-F , FACT-ES , and BFI global scores compared to placebo on days 21 and 49 ( p < 0.01 ) . The Chalder Scale improved significantly on day 21 ( p < 0.01 ) but not on day 49 ( p = 0.27 ) . Guarana did not produce any Common Terminology Criteria for Adverse Events grade s 2 , 3 , or 4 toxicities and did not worsen sleep quality or cause anxiety or depression . CONCLUSIONS Guarana is an effective , inexpensive , and nontoxic alternative for the short-term treatment of fatigue  in BC patients receiving systemic chemotherapy . Further studies are needed to confirm these results and to evaluate their generalizability to chronic CRF and to other types of cancer BACKGROUND Safe , effective interventions to improve cancer-related fatigue ( CRF ) are needed because it remains a prevalent , distressing , and activity-limiting symptom . Based on pilot data , a phase III trial was developed to evaluate the efficacy of American ginseng on CRF . METHODS A multisite , double-blind trial r and omized fatigued cancer survivors to 2000 mg of American ginseng vs a placebo for 8 weeks . The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) at 4 weeks . Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided , two- sample t test . Toxicities were evaluated by self-report and the National Cancer Institute 's Common Terminology Criteria for Adverse Events ( CTCAE ) provider grading . RESULTS Three hundred sixty-four participants were enrolled from 40 institutions . Changes from baseline in the general subscale of the MFSI-SF were 14.4 ( st and ard deviation [ SD ] = 27.1 ) in the ginseng arm vs 8.2 ( SD = 24.8 ) in the placebo arm at 4 weeks ( P = .07 ) . A statistically significant difference was seen at 8 weeks with a change score of 20 ( SD = 27 ) for the ginseng group and 10.3 ( SD = 26.1 ) for the placebo group ( P = .003 ) . Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment . Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms . CONCLUSIONS Data support the benefit of American ginseng , 2000 mg daily , on CRF over an 8-week period . There were no discernible toxicities associated with the treatment . Studies to increase knowledge to guide the role of ginseng to improve CRF are needed PURPOSE To evaluate the effectiveness of patient-controlled methylpheni date as compared with placebo in cancer patients with fatigue  , as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue ( FACIT-F ) . PATIENTS AND METHODS Patients with a fatigue score of at least 4 on a scale of 0 to 10 ( 0 = no fatigue , 10 = worst possible fatigue ) and hemoglobin level of at least 10 g/dL were included . Patients were r and omly assigned to receive 5 mg methylpheni date or placebo every 2 hours as needed ( maximum of four capsules a day ) , for 7 days . Patients completed a daily diary including study drug record and fatigue intensity . A research nurse telephoned patients daily to assess toxicity and fatigue level . All patients were offered open-label methylpheni date for 4 weeks . FACIT-F and the Edmonton Symptom Assessment System ( ESAS ) were assessed at baseline , and days 8 , 15 , and 36 . The FACIT-F fatigue subscore on day 8 was considered the primary end point . RESULTS Of 112 patients r and omly assigned , 52 patients in the methylpheni date and 53 in the placebo group were assessable for analysis . Fatigue intensity improved significantly on day 8 in both the methylpheni date and placebo groups . However , there was no significant difference in fatigue improvement by FACIT-F ( P = .31 ) or ESAS ( P = .14 ) between groups . In open-label phase , fatigue intensity maintained low as compared with baseline . No significant toxicities were observed . CONCLUSION Both methylpheni date and placebo result ed in significant symptom improvement .  Methylpheni date was not significantly superior to placebo after 1 week of treatment . Longer study duration is justified . The role of daily telephone calls from a research nurse should be explored as a palliative care intervention PURPOSE To evaluate the effectiveness of donepezil compared with placebo in cancer patients with fatigue as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue ( FACIT-F ) . PATIENTS AND METHODS Patients with fatigue score > or= 4 on a scale of 0 to 10 ( 0 = no fatigue , 10 = worst possible fatigue ) for more than 1 week were included . Patients were r and omly assigned to receive donepezil 5 mg or placebo orally every morning for 7 days . A research nurse contacted the patients by telephone daily to assess toxicity and fatigue level . All patients were offered open-label donepezil during the second week . FACIT-F and /or the Edmonton Symptom Assessment System ( ESAS ) were assessed at baseline , and days 8 , 11 , and 15 . The FACIT-F fatigue subscale score on day 8 was considered the primary end point . RESULTS Of 142 patients r and omly assigned to treatment , 47 patients in the donepezil group and 56 in the placebo group were assessable for final analysis . Fatigue intensity improved significantly on day 8 in both donepezil and placebo groups . However , there was no significant difference in fatigue improvement by FACIT-F ( P = .57 ) or ESAS ( P = .18 ) between groups . In the open-label phase , fatigue intensity continued to be low as compared with baseline . No significant toxicities were observed . CONCLUSION Donepezil was not significantly superior to placebo in the treatment of cancer-related fatigue Cancer-related fatigue is a substantial problem for cancer patients and their caregivers , but no effective treatment exists . Acupuncture has been suggested to improve cancer-related fatigue , but no r and omized clinical trials have been conducted . We hypothesized that true acupuncture , compared with sham acupuncture , would reduce cancer-related fatigue in cancer patients receiving external radiation therapy .  The aim of this study was to determine effect size and feasibility . A modified , double-blind , r and omized , placebo-controlled trial was conducted . The subject , clinical staff , and assessor were blinded , but the acupuncturist was not . Subjects received acupuncture once to twice per week during the 6-week course of radiation therapy . Data were collected at baseline , 3 weeks , 6 weeks , and 10 weeks , which was 4 weeks after that last radiation session . Twenty-seven subjects enrolled , and 23 completed the last data collection . Both true and sham acupuncture groups had improved fatigue , fatigue distress , quality of life , and depression from baseline to 10 weeks , but the differences between the groups were not statistically significant . The true acupuncture group improved 5.50 ( SE , + /- 1.48 ) points on the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale ( FACIT-F ) , whereas the sham acupuncture group improved by 3.73 ( SE + /- 1.92 ) points . This difference was not statistically significant ( p = .37 ) . All subjects guessed that they were in the true acupuncture group . Our study was underpowered to find a statistically significant difference . To demonstrate a statistically significant improvement between true and sham acupuncture would require 75 subjects per group in a future study . Owing to poor recruitment , the feasibility of a larger trial using the same methodology is low . Despite being underpowered , it appears that subjects receiving true acupuncture may benefit more than subjects receiving sham acupuncture . In the discussion section , we review our experience with using a sham-needle controlled study PURPOSE Cancer-related fatigue ( CRF ) is the most common symptom in patients with advanced cancer . The primary objective of this prospect i ve , r and omized , double-blind , placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF . PATIENTS AND METHODS Patients with advanced cancer with ≥ three CRF-related symptoms ( ie , fatigue , pain , nausea , loss of appetite , depression , anxiety , or sleep disturbance ) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale ( ESAS ) were eligible . Patients were r and omly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days . The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue ( FACIT-F ) subscale from baseline to day 15 . Secondary outcomes included anorexia , anxiety , depression , and symptom distress scores . RESULTS A total of 84 patients were evaluable  ( dexamethasone , 43 ; placebo , 41 ) . Mean ( ± st and ard deviation ) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group ( 9 [ ± 10.3 ] v 3.1 [ ± 9.59 ] ; P = .008 ) . The improvement in FACIT-F total quality -of-life scores was also significantly better for the dexamethasone group at day 15 ( P = .03 ) . The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group ( P = .013 , respectively ) . No differences were observed for ESAS overall symptom distress ( P = .22 ) or psychological distress score ( P = .76 ) . Frequency of adverse effects was not significantly different between groups ( 41 of 62 v 44 of 58 ; P = .14 ) . CONCLUSION Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer Fatigue is very common in patients with cancer . Current guidelines suggest that psychostimulants are " reasonable to consider for severe fatigue . " This r and omized , double-blind , placebo-controlled trial investigated the hypothesis that  dexamphetamine  in fatigued patients with advanced cancer would produce a clinical ly significant improvement with minimal side effects . Fifty patients with advanced cancer , who were receiving palliative care , were r and omized to dexamphetamine 10 mg twice daily or placebo for eight days . Effectiveness was assessed using the Brief Fatigue Inventory and the McGill Quality -of-Life Question naire . The side effects were recorded . The results were analyzed on an intention-to-treat basis . The baseline demographics , fatigue levels , and quality -of-life scores were similar between the two arms . Patients were elderly , had impaired performance status ( Eastern Cooperative Oncology Group score=3 ) , and were taking a range of neurologically active medications . Thirty-nine patients completed the trial . There was a transient improvement in the fatigue levels on day 2 , but no significant difference in fatigue ( P=0.267 ) or quality of life ( P=0.579 ) by the end of the study . Statistical modeling did not reveal any significant predictors of response to dexamphetamine . These results suggest that dexamphetamine 20 mg daily , although well tolerated , does not significantly improve fatigue or quality of life in patients with advanced cancer , as measured by the selected instruments BACKGROUND Depression , anxiety , fatigue , and impaired wellbeing are common , important , and closely related in advanced cancer . We aim ed to identify the effects of an established antidepressant on these symptoms and survival in patients with advanced cancer who did not have major depression as assessed by clinicians . METHODS Between July , 2001 , and February , 2006 , 189 patients with advanced cancer were r and omly assigned sertraline 50 mg ( n=95 ) , or placebo ( n=94 ) , once per day . The primary outcome was depression as assessed by the Centre for Epidemiologic Studies Depression scale ( CES-D ) ; the main secondary outcomes were : anxiety as assessed by Hospital Anxiety and Depression Scales ( HADS-A ) ; overall quality of life and fatigue as assessed by Functional Assessment of Cancer Therapy General and Fatigue scales ( FACT-G and FACT-F , respectively ) ; and clinicians ' ratings of quality of life by use of Spizter 's Quality of Life Index ( SQLI ) . Multiple measures were used for corroboration of the most important outcomes . Primary analyses were done by intention to treat and were based on scale scores at 4 weeks and 8 weeks . The benefits of sertraline compared with placebo are expressed on a range from + 100 ( ie , maximum benefit ) to -100 ( ie , maximum harm ) ; a difference of 10 was deemed clinical ly significant . This clinical trial is registered at Current Controlled Trials website http://www.controlled-trials.com/IS RCT N72466475 . FINDINGS Sertraline had no significant effect ( scale , benefit over placebo [ 95 % CI ] ) on depression ( CES-D 0.4 [ -2.6 to 3.4 ] ) , anxiety ( HADS-A 2.0 [ -1.5 to 5.5 ] ) , fatigue ( FACT-F 0.3 [ -4.3 to 4.9 ] ) , overall quality of life ( FACT-G 1.7 [ -1.3 to 4.7 ] ) , or clinicians ' ratings ( SQLI 2.0 [ -2.5 to 6.5 ] ) , and the 95 % CI ruled out a clinical ly significant benefit for all main outcomes . Sertraline was discontinued more often and earlier than was placebo ( hazard ratio 1.46 [ 1.03 - 2.06 ] , p=0.03 ) . Recruitment was stopped after the first planned interim analysis in February 2006 ( n=150 ) showed that survival was longer in patients assigned placebo than in patients assigned sertraline ( unadjusted hazard ratio 1.60 [ 95 % CI 1.04 - 2.45 ] , log-rank p=0.04 ; adjusted hazard ratio 1.62 [ 1.06 - 2.41 ] , Cox model p=0.02 ) . However , at the final analysis in July 2006 of all patients ( n=189 ) and with longer follow-up , survival did not differ significantly between the treatment groups ( unadjusted hazard ratio 1.35 [ 0.95 - 1.91 ] , log-rank p=0.09 ; adjusted hazard ratio 1.27 [ 0.87 - 1.84 ] , Cox model p=0.20 ) . The trial was closed because it had ruled out a significant benefit of sertraline . INTERPRETATION Sertraline did not improve symptoms , wellbeing , or survival in patients with advanced cancer who do not have major depression , and should be reserved for those with a proven indication PURPOSE Cancer-related-fatigue ( CRF ) is common in advanced cancer . The primary objective of the study was to compare the effects of methylpheni date ( MP ) with those of placebo ( PL ) on CRF as measured using the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) fatigue subscale . The effect of a combined intervention including MP plus a nursing telephone intervention ( NTI ) was also assessed . PATIENTS AND METHODS Patients with advanced cancer with a fatigue score of ≥ 4 out of 10 on the Edmonton Symptom Assessment Scale ( ESAS ) were r and omly assigned to one of the following four groups : MP+NTI , PL+NTI , MP + control telephone intervention ( CTI ) , and PL+CTI . Methylpheni date dose was 5 mg every 2 hours as needed up to 20 mg per day . The primary end point was the median difference in FACIT-F fatigue at day 15 . Secondary outcomes included anxiety , depression , and sleep . RESULTS One hundred forty-one patients were evaluable . Median FACIT-F fatigue scores improved from baseline to day 15 in all groups : MP+NTI ( median score , 4.5 ; P = .005 ) , PL+NTI ( median score , 8.0 ; P < .001 ) , MP+CTI ( median score , 7.0 ; P = .004 ) , and PL+CTI ( median score , 5.0 ; P = .03 ) . However , there were no significant differences in the median improvement in FACIT-F fatigue between the MP and PL groups ( 5.5 v 6.0 , respectively ; P = .69 ) and among all four groups ( P = .16 ) . Fatigue ( P < .001 ) , nausea ( P = .01 ) , depression ( P = .02 ) , anxiety ( P = .01 ) , drowsiness ( P < .001 ) , appetite ( P = .009 ) , sleep ( P < .001 ) , and feeling of well-being ( P < .001 ) , as measured by the ESAS , significantly improved in patients who received NTI . Grade ≥ 3 adverse events did not differ between MP and PL ( 40 of 93 patients v 29 of 97 patients , respectively ; P = .06 ) . CONCLUSION MP and NTI alone or combined were not superior to placebo in improving CRF Abstract Background : Cancer-related fatigue ( CRF ) is the most common and distressing symptom associated with cancer treatment that breast cancer survivors ( BCS ) experience . We previously found that laser moxibustion may be efficacious for CRF . The primary aim of this study is to determine the specific efficacy of 10.6 μm infrared laser moxibustion on CRF . The secondary aim is to evaluate the effect of infrared laser moxibustion on co-existing symptoms that BCS experience . Methods : We will conduct a r and omized , sham-controlled , three-arm trial of infrared laser moxibustion ( ILM ) against sham ILM ( SILM ) and waitlist control ( WLC )  among BCS with moderate to severe fatigue . The two intervention groups will receive either real or sham infrared laser moxibustion on four acupoints ( i.e. , ST36 [ bilateral ] , CV4 , and CV6 ) for 20 minutes each session for 6 weeks ( twice per week ) . The primary endpoint is the change in fatigue score from Baseline to Week 6 as measured by the Chinese version of the Brief Fatigue Inventory ( BFI-C ) . Our secondary aim is to compare the severity of co-morbidities ( e.g. , depression , insomnia , and pain ) among the 3 groups . Discussion : The results of our trial will establish evidence for the efficacy of infrared laser moxibustion for CRF , a very common and challenging symptom . Trial registration number : NCT03553355 The purpose of this 21-day assessor blinded , r and omized-controlled trial was to compare an open-label placebo ( OLP ) to treatment as usual ( TAU ) for cancer survivors with fatigue . This was followed by an exploratory 21-day study in which TAU participants received OLPs while OLP participants in the main study were followed after discontinuing placebos . Cancer survivors ( N = 74 ) who completed cancer treatment 6 months to 10 years prior to enrollment reporting at least moderate fatigue ( i.e. , ≥4 on a 0–10 scale ) were r and omized to OLP or TAU . Those r and omized to OLP took 2 placebo pills twice a day for 21 days . Compared to those r and omized to TAU , OLP participants reported a 29 % improvement in fatigue severity ( average difference in the mean change scores ( MD ) 12.47 , 95 % CI 3.32 , 21.61 ; P = 0.008 ) , medium effect ( d = 0.63 ) , and a 39 % improvement in fatigue-disrupted quality of life ( MD = 11.76 , 95 % CI 4.65 , 18.86 ; P = 0.002 ) , a large effect ( d = 0.76 ) . TAU participants who elected to try OLP for 21-days after the main study reported reductions in fatigue of a similar magnitude for fatigue severity and fatigue-disrupted quality of life ( 23 % and 35 % , respectively ) . OLP may reduce fatigue symptom severity and fatigue-related quality of life disruption in cancer survivors
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 research ers in design ing future clinical trials for the treatment of CRF .