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The aim of this study was to evaluate a low-dose regimen of megestrol acetate ( MA ; 320 mg/day ) on appetite in advanced cancer patients . Out- patients with far-advanced non-hormone responsive tumours and loss of appetite were r and omised in a phase III trial , with two consecutive phases : a 14-day double-blind placebo controlled phase ( phase A ) and a 76-day open phase ( phase B ) . During phase A , patients were treated with MA , two 160 mg tablets/day , or placebo . In phase B , the MA dose was titrated to clinical response in both groups . Appetite , food intake , body weight , performance status , mood and quality of life were evaluated with st and ardised measures ; patients ' global judgement about treatment efficacy was also requested . Of 42 patients entering the study , 33 ( 17 MA and 16 placebo ) were evaluable for efficacy . The appetite score improved significantly with MA after 7 days ( P = 0.0023 ) , and this effect was still significant at 14 days ( P = 0.0064 ) . Patients judged the treatment with MA effective in 88.2 % of cases ( 14th day ) , whilst placebo was considered effective by 25 % ( P = 0.0003 ) . None of the other measures showed significant changes during treatment . The remarkable effect on appetite evident after 7 days , without serious side-effects , shows that MA can produce significant subjective effects at a low-dose even in patients with far-advanced disease Patients with breast cancer treated with adjuvant chemotherapy  experience not only fatigue and menopausal symptoms but also documented cognitive dysfunction and reduced capacity to carry out activities of daily living . The role of epoetin alfa in improving cognition and functional capacity was assessed in a large r and omized trial through patient self-reported outcomes . Patients with breast cancer ( N = 354 , adjuvant and metastatic ) undergoing chemotherapy  were r and omized in a 1:1 ratio to receive epoetin alfa ( 40,000 IU once weekly ) or the st and ard of care ( SOC ) . Change in patient-reported Health Utilities Index Mark 3 ( HUI3 ) from baseline to week 12 was compared between the epoetin alfa and SOC groups . In addition , correlations between the disease-nonspecific HUI3 utility scale and the cancer-specific quality of life instrument Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) and Fatigue subscales were assessed . Epoetin alfa treatment significantly improved HUI3 scores compared with patients receiving SOC ( P = 0.036 ) . Three subscales within HUI3 were also significantly better for epoetin alfa-treated patients ( emotion , P = 0.048 ; ambulation , P = 0.048 ; and cognition , P = 0.02 ) . Moreover , a strong correlation ( P = 0.0001 ) exists between the disease-nonspecific utility scale HUI3 and the disease-specific FACT-An and FACT-Fatigue scales in terms of overall scores and score changes . The findings of the study demonstrate for the first time in patients with breast cancer that epoetin alfa significantly enhances functional well-being , which translates into significantly better utility scores . In addition , epoetin alfa also significantly improved cognitive function of women undergoing chemotherapy , and this could have an important impact on their lives from a societal perspective BACKGROUND Bojungikki-tang ( Bu-Zhong-Yi-Qi-Tang in Chinese or Hochu-ekki-to in Japanese ) is a widely used herbal prescription in traditional medicine in China , Japan , and Korea . The aim of this study was to investigate the effectiveness of Bojungikki-tang for cancer-related fatigue . METHODS A total of 40 patients with cancer-related fatigue were r and omized into an experimental or a waiting list control group . Patients in the experimental group were treated with Bojungikki-tang ( TJ-41 ) and patients in the waiting list group remained without any intervention for 2 weeks . RESULTS The experimental group showed statistically significant improvements in fatigue level assessed by the Visual Analogue Scale of Global Fatigue ( VAS-F ) measuring the severity of fatigue ( experimental vs control : -1.1 ± 2.1 vs 0.1 ± 0.9 , P < .05 ) and results of Functional Assessment of Cancer Therapy-General ( FACT-G ) , Functional Assessment of Cancer Therapy-Fatigue ( FACT-F ) , and Trial Outcome Index-Fatigue ( TOI-F ) also showed significant improvements ( FACT-G , 3.7 ± 9.9 vs -2.4 ± 9.5 , P < .05 ; FACT-F , F , 8.0 ± 13.6 vs -2.2 ± 14.1 , P < .05 ; TOI-F , 6.5 ± 9.2 vs -0.5 ± 10.9 , P < .05 ) . CONCLUSIONS The results of this study indicate that Bojungikki-tang may have beneficial effects on cancer-related fatigue and quality of lives in cancer patients . More rigorous trials are needed to confirm the efficacy of Bojungikki-tang BACKGROUND Extracellular adenosine 5'-triphosphate ( ATP ) is involved in the regulation of a variety of biologic processes , including neurotransmission , muscle contraction , and liver glucose metabolism , via purinergic receptors . In nonr and omized studies involving patients with different tumor types including non-small-cell lung cancer ( NSCLC ) , ATP infusion appeared to inhibit loss of weight and deterioration of quality of life ( QOL ) and performance status . We conducted a r and omized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC ( stage IIIB or IV ) . METHODS Fifty-eight patients were r and omly assigned to receive either 10 intravenous 30-hour ATP infusions , with the infusions given at 2- to 4-week intervals , or no ATP . Outcome parameters were assessed every 4 weeks until 28 weeks . Between-group differences were tested for statistical significance by use of repeated- measures analysis , and reported P values are two-sided . RESULTS Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP .  Mean weight changes per 4-week period were -1.0 kg ( 95 % confidence interval [ CI ] = -1.5 to -0.5 ) in the control group and 0.2 kg ( 95 % CI = -0.2 to + 0.6 ) in the ATP group ( P = .002 ) . Serum albumin concentration declined by -1.2 g/L ( 95 % CI= -2.0 to -0.4 ) per 4 weeks in the control group but remained stable ( 0.0 g/L ; 95 % CI = -0.3 to + 0.3 ) in the ATP group ( P = .006 ) . Elbow flexor muscle strength declined by -5.5 % ( 95 % CI = -9.6 % to -1 . 4 % ) per 4 weeks in the control group but remained stable ( 0.0 % ; 95 % CI= -1.4 % to + 1.4 % ) in the ATP group ( P = .01 ) . A similar pattern was observed for knee extensor muscles ( P = .02 ) . The effects of  ATP  on body weight , muscle strength , and albumin concentration were especially marked in cachectic patients ( P = .0002 , P = .0001 , and P = . 0001 , respectively , for ATP versus no ATP ) . QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical scores ( -0.2 % versus -2.4 % ; P = . 0002 ) ; functional scores ( + 0.4 % versus -5.5 % ; P = .02 ) ; psychologic scores ( -0.7 % versus -2.4 % ; P = .11 ) ; overall QOL score ( + 0.1 % versus -3.5 % ; P = .0001 ) . CONCLUSIONS This r and omized trial demonstrates that ATP has beneficial effects on weight , muscle strength , and QOL in patients with advanced NSCLC Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients . An open-label , r and omized , pilot trial examined both the general and differential efficacy of 4 weeks of methylpheni date ( MPH ) and modafinil ( MOD ) in 24 brain tumor patients . Participants completed cognitive tests and self-report measures of fatigue , sleep disturbance , mood and quality of life at baseline and after 4 weeks . Following stimulant treatment , there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention . Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy . Inconsistent , differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD . There was also evidence of a general beneficial effect on patient-reported measures of fatigue , mood , and quality of life , with no statistically significant differences between treatment arms in these measures over time . The results from this small pilot study should be interpreted with caution , but appear to warrant additional research , in larger study sample s , targeting fatigue , processing speed and executive function , and exploring different doses of stimulants . Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment PURPOSE To investigate the effect of recombinant human erythropoietin ( epoetin beta ) on anemia , transfusion need , and quality of life ( QOL ) in severely anemic patients with low- grade non-Hodgkin 's lymphoma ( NHL ) , chronic lymphocytic leukemia ( CLL ) , or multiple myeloma ( MM ) . PATIENTS AND METHODS Transfusion-dependent patients with NHL ( n = 106 ) , CLL ( n = 126 ) , or MM ( n = 117 ) and a low serum erythropoietin concentration were r and omized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks . Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival ( hemoglobin [ Hb ] > 8.5 g/dL ) between weeks 5 to 16 . Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need . QOL was assessed by the Functional Assessment of Cancer Therapy scale . RESULTS Transfusion-free ( P = .0012 ) survival and transfusion- and severe anemia-free survival ( P = .0001 ) were significantly greater in the epoetin beta group versus placebo ( Wald chi(2 ) test ) , giving a relative risk reduction of 43 % and 51 % , respectively . The response rate was 67 % and 27 % in the epoetin beta versus the placebo group , respectively ( P < .0001 ) . After 12 and 16 weeks of treatment , QOL significantly improved in the epoetin beta group compared with placebo ( P < .05 ) ; this improvement correlated with an increase in Hb concentration ( > or = 2 g/dL ) . A target Hb that could be generally recommended could not be identified . CONCLUSION Many severely anemic and transfusion-dependent patients with advanced MM , NHL , and CLL and a low performance status benefited from epoetin therapy , with elimination of severe anemia and transfusion need , and improvement in QOL 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 Sleep disorders are a substantial problem for cancer survivors , with prevalence estimates ranging from 23 % to 61 % . Although numerous prescription hypnotics are available , few are approved for long-term use or have demonstrated benefit in this circumstance . Hypnotics may have unwanted side effects and are costly , and cancer survivors often wish to avoid prescription drugs . New options with limited side effects are needed . The purpose of this trial was to evaluate the efficacy of a Valerian officinalis supplement for sleep in people with cancer who were undergoing cancer treatment . Participants were r and omized to receive 450 mg of valerian-or placebo orally 1 hour before bedtime for 8 weeks . The primary end point was area under the curve ( AUC ) of the overall Pittsburgh Sleep Quality Index ( PSQI ) . Secondary outcomes included the Functional Outcomes of Sleep Question naire , the Brief Fatigue Inventory ( BFI ) , and the Profile of Mood States ( POMS ) . Toxicity was evaluated with both self-reported numeric analogue scale questions and the Common Terminology Criteria for Adverse Events ( CTCAE ) , version 3.0 . Question naires were completed at baseline and at 4 and 8 weeks . A total of 227 patients were r and omized into this study between March 19 , 2004 , and March 9 , 2007 , with 119 being evaluable for the primary end point . The AUC over the 8 weeks for valerian was 51.4 ( SD = 16 ) , while that for placebo was 49.7 ( SD = 15 ) , with a P value of 0.6957 . A supplemental , exploratory analysis revealed that several fatigue end points , as measured by the BFI and POMS , were significantly better for those taking valerian over placebo . Participants also reported less trouble with sleep and less drowsiness on valerian than placebo . There were no significant differences in toxicities as measured by self-report or the CTCAE except for mild alkaline phosphatase increases , which were slightly more common in the placebo group . This study failed to provide data to support the hypothesis that valerian , 450 mg , at bedtime could improve sleep as measured by the PSQI . However , exploratory analyses revealed improvement in some secondary outcomes , such as fatigue . Further research with valerian exploring physiologic effects in oncology symptom management may be warranted A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly ( QW ) , every 3 weeks ( Q3W ) , and every 4 weeks ( Q4W ) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy . The QW portion ( n=102 ) was an open-label , sequential , dose-escalation design ; cohorts received darbepoetin alpha QW by subcutaneous ( s.c . ) injection at 0.5 , 1.0 , 2.25 , or 4.5 μg kg−1 week−1 for 12 weeks . The 12-week placebo-controlled , double – blind Q3W ( 6.75 μg kg−1 ) and Q4W ( 6.75 or 10.0 μg kg−1 ) schedules ( n=86 ) , which enrolled different patients , took place after the QW schedule and were followed by a 12-week , open-label phase . Patients were evaluated for change in haemoglobin end points and red blood cell transfusions , serum darbepoetin alpha concentration , and safety . Selected domains of health-related quality of life ( HRQOL ) were measured . With QW dosing , at least 70 % of each cohort had a haemoglobin increase from baseline of ⩾2 g dl−1 or a concentration ⩾12 g dl−1 ( haematopoietic response ) . In the 4.5 μg kg−1 QW cohort , all patients achieved a haematopoietic response ( 100 % ; 95 % confidence interval (CI)=100 , 100 ) . In the Q3W and Q4W schedules , all cohorts had at least 60 % of patients who achieved a haematopoietic response .  Darbepoetin alpha effectively increases haemoglobin concentration when given QW , Q3W , or Q4W . Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike This multicentre , open-label , controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life ( QOL ) parameters in 182 anaemic ( Hb⩽12 g dl−1 ) ovarian cancer patients receiving platinum chemotherapy . Patients were r and omised 2 : 1 to receive epoetin alfa 10 000–20 000 IU three times weekly plus best st and ard treatment ( BST ) or BST only . Main study end points were changes from baseline in haemoglobin ( Hb ) level , transfusion requirements , and QOL . For the epoetin alfa group , mean Hb increased by 1.8 g dl−1 by weeks 4–6 and was significantly increased from baseline through study end ( P<0.001 ) . The mean change in Hb from baseline was significantly ( P<0.001 ) greater for epoetin alfa than BST patients at all postbaseline evaluations . Significantly fewer epoetin alfa than BST patients required transfusion(s ) after the first 4 weeks of treatment ( 7.9 vs 30.5 % ; P<0.001 ) . Also , significant ( P⩽0.04 ) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores ( Energy Level , Ability to Do Daily Activities , Overall QOL ) and the median average CLAS score during chemotherapy . These findings support use of epoetin alfa to increase Hb levels , reduce transfusion use , and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy Summary Background . Fatigue can significantly interfere with a cancer patient ’s ability to fulfill daily responsibilities and enjoy life . It commonly co-exists with depression in patients undergoing chemotherapy , suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue . Methods . We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy r and omly assigned to receive either  20 mg of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine ( Paxil ® , SmithKline Beecham Pharmaceuticals ) or an identical-appearing placebo . Patients began their study medication seven days following their first on- study treatment and continued until seven days following their fourth on- study treatment . Seven days after each treatment , participants completed question naires measuring fatigue ( Multidimensional Assessment of Fatigue , Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist ) and depression ( Profile of Mood States-Depression subscale [ POMS-DD ] and Center for Epidemiologic Studies -Depression [ CES-D ] ) . Results . Repeated- measures ANOVAs , after controlling for baseline measures , showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D ( p=0.006 ) and the POMS-DD ( p=0.07 ) but not in reducing fatigue ( all measures , ps > 0.27 ) . Conclusions . Although depression was significantly reduced in the 44 patients receiving paroxetine  compared to the 50 patients receiving placebo , indicating that a biologically active dose was used , no significant differences between groups on any of the measures of fatigued were observed . Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment Background Cancer-related fatigue ( CRF ) is experienced by 50 % to 90 % of cancer patients and can severely affect their quality of life and functional capacity . Several r and omized trials have recommended various ways to alleviate the symptoms of CRF with or without recourse to medications . Objective The aim of this study is to evaluate the effectiveness of processed honey and royal jelly on the symptoms of CRF in cancer patients who are undergoing hormone therapy , chemotherapy , chemo-radiation , or radiotherapy . Methods Fifty-two participants from the patients who visited the oncology clinic of Shohada-e-Tajrish hospital in Tehran ( Iran ) between May 2013 and August 2014 were selected and divided into two groups . The study group ( 26 patients ) received processed honey and royal jelly , while the control group received pure honey . Both groups were instructed to consume their 5mL supplement twice daily for 4 weeks . Both groups were assessed at the beginning of the study , after 2 weeks , and then at the end of 4 weeks of treatment . Fatigue was measured using a visual analogue fatigue scale ( VAFS ) and fatigue severity scale ( FSS ) . The results were compared between the two arms of study , and e quality of probability distributions was assessed using a Kolmogorov – Smirnov test . Results The mean age of the 52 patients was 54.84 . After two and four weeks of treatment with processed honey and royal jelly , VAFS and FSS due to treatment was better in the study group than in the control group , and the differences were statistically significant ( p<0.001 , p<0.001 , respectively ) . Conclusion To the best of our knowledge , our study provided support for the use of processed honey and royal jelly to ameliorate CRF . The positive results of this study warrant further studies in this field . Clinical Trial Registration The study was registered in the Iranian Clinical Trial Registry Center ( http://www.i rct .ir ) with the registration code : I RCT 2015081423426N1 . Funding The authors received no financial support for the research , authors hip , and /or publication of this article PURPOSE To determine whether weekly epoetin alfa could improve hemoglobin ( HgB ) levels , reduce RBC transfusions , and improve quality of life ( QOL ) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy . PATIENTS AND METHODS This double-blind , placebo-controlled study r and omly assigned patients to placebo or epoetin alfa ( Ortho Biotech , Bridgewater , NJ ) 40,000 U subcutaneous weekly for 16 weeks . QOL , HgB , and RBC transfusions were measured pretreatment and monthly . RESULTS The study accrued 344 patients ; 330 were assessable for efficacy and 305 were assessable for QOL .  Placebo-treated patients had a mean increase in HgB of 0.9 g/dL ( range , -3.8 to + 5.3 ) compared with 2.8 g/dL ( range , -2.2 to + 7.5 ) for epoetin-treated patients ( P < .0001 ) . During the study , 31.7 % of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7 % of epoetin-treated patients ( P < .0001 ) . The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6 % and 25.3 % ( P = .005 ) , respectively . The placebo group received 256 units of RBCs compared with 127 units in the epoetin group ( P < .0001 ) . The incidence of toxicity in the groups was similar . Changes in the average QOL scores from baseline to the end of the study were similar in the two groups ( P = not significant ) . The HgB responders ( irrespective of treatment arm ) had a mean change in Functional Assessment of Cancer Therapy ( FACT ) fatigue score from a baseline of + 5.1 compared with -2.1 for the nonresponders ( P = .006 ) . CONCLUSION Epoetin alfa significantly improved HgB and reduced transfusions in this patient population . These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia PURPOSE Maintaining dose-intensity with chemotherapeutic agents is hindered by a number of adverse effects including asthenia/fatigue . Tumor necrosis factor ( TNF ) is one of the cytokines responsible for the fatigue and cachexia associated with malignancies . We used etanercept ( TNF-decoy receptor ) to maintain dose-intensity of weekly docetaxel . PATIENTS AND METHODS Initially , 12 patients with advanced malignancies were r and omly assigned to either docetaxel 43 mg/m2 weekly alone ( cohort A ) or the same docetaxel dose plus etanercept 25 mg subcutaneously twice weekly ( cohort B ) . Subsequently , higher doses of docetaxel in combination with etanercept were evaluated . Pharmacokinetics ( PKs ) , nuclear factor-kappa B ( NF-kappaB ) activation , and intracellular cytokines levels were measured . Patients completed weekly question naires quantifying asthenia/fatigue . RESULTS Twenty-nine of 36 intended docetaxel doses during the first cycle were delivered in cohort A , and 35 of 36 doses were delivered in cohort B ( P = .055 ) . Three cohort B patients received additional cycles in the absence of disease progression or severe toxicity , whereas no patients from cohort A received additional cycles . Escalation to docetaxel 52 mg/m2 weekly with etanercept result ed in neutropenia , not fatigue , as the limiting adverse effect , and the addition of filgrastim permitted the maintenance of dose-intensity in additional patients . Patients r and omly selected to receive etanercept/docetaxel self-reported less fatigue ( P < .001 ) , and docetaxel PKs show no relevant influence of etanercept . NF-kappaB activation and increased expression of TNF-alpha were associated with increments in docetaxel dose . Antitumor activity was noticed exclusively in patients receiving etanercept . CONCLUSION The addition of etanercept is safe and had no impact on docetaxel concentrations . The significant improvement in tolerability and the trend toward preservation of dose-intensity suggests further exploration of TNF blockade as an adjunct to cancer therapies 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 Background Chemotherapy for breast cancer often deteriorates quality of life , augments fatigue , and induces neutropenia .  Mistletoe preparations are frequently used by cancer patients in Central Europe . Physicians have reported better quality of life in breast cancer patients additionally treated with mistletoe preparations during chemotherapy . Mistletoe preparations also have immunostimulant properties and might therefore have protective effects against chemotherapy-induced neutropenia . Patients and Methods We conducted a prospect i ve r and omized open label pilot study with 95 patients r and omized into three groups . Two groups received Iscador ® M special ( IMS ) or a different mistletoe preparation , respectively , additionally to chemotherapy with six cycles of cyclophosphamide , adriamycin , and 5-fluoro-uracil ( CAF ) . A control group received CAF with no additional therapy . Here we report the comparison IMS ( n = 30 ) vs. control ( n = 31 ) . Quality of life including fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC-QLQ-C30 ) . Neutropenia was defined as neutrophil counts < 1,000/μl and assessed at baseline and one day before each CAF cycle . Results In the descriptive analysis all 15 scores of the EORTC-QLQ-C30 showed better quality of life in the IMS group compared to the control group . In 12 scores the differences were significant ( p < 0.02 ) and nine scores showed a clinical ly relevant and significant difference of at least 5 points . Neutropenia occurred in 3/30 IMS patients and in 8/31 control patients ( p = 0.182 ) . Conclusions This pilot study showed an improvement of quality of life by treating breast cancer patients with IMS additionally to CAF . CAF-induced neutropenia showed a trend to lower frequency in the IMS group The prevention of post-chemotherapy symptoms such as delayed emesis , anorexia , and fatigue induced by irinotecan has not been studied . We compared the effects of dexamethasone ( Dex ) with those of a placebo on these symptoms in a r and omized study . Seventy patients scheduled to receive irinotecan chemotherapy  were enrolled in the study and r and omly divided into a treatment or a placebo group . In the treatment group , 8 mg of Dex were administered on days 2–4 after the start of chemotherapy . All patients in both groups received Dex and granisetron for prophylaxis against acute emesis on day 1 . We evaluated 68 patients ( 35 receiving Dex , 33 receiving the placebo ) .  Although delayed emesis was completely prevented in most of patients in both groups ( Dex , 82.9 % ; placebo , 78.8 % ) , anorexia and fatigue were more completely prevented in those in the Dex group ( Dex , 62.9 % and 77.1 % , placebo , 39.4 % and 57.6 % , respectively ) . The effect of Dex on improving simultaneous prophylaxis against all three symptoms was almost significant ( Dex , 60.0 % ; placebo , 36.4 % ; P=0.058 ) . The safety profiles of the two groups were not discernibly different . These results suggest that treatment with Dex may be beneficial to reduce post-chemotherapy symptoms induced by irinotecan , specifically anorexia and fatigue , with acceptable toxicities OBJECTIVE To determine a recommended dose of once-weekly epoetin-beta administration for anemic cancer patients receiving myelosuppressive chemotherapy , we conducted a multicenter , r and omized , double-blind trial . METHODS A total of 86 patients with malignant lymphoma or lung cancer who received chemotherapy containing platinum , taxanes or anthracyclines were enrolled in the study . Patients were r and omly assigned into groups that received three dose levels of epoetin-beta ( 9000 , 18,000 or 36,000 IU ) administered subcutaneously once a week for 12 weeks . The primary endpoint was change in hemoglobin , while the secondary endpoints were quality of life ( QOL ) assessed by Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) question naire and transfusion requirements . RESULTS Among the 69 patients ( per protocol set population ) assessable for efficacy , hemoglobin level change in the 36,000 IU group was significantly greater than that in the 9000 IU group ( 1.75 + /- 2.15 versus 0.04 + /- 1.98 g/dl ; P = 0.009 ) , and a significant dose-response relationship was observed for the change in hemoglobin level ( P = 0.003 ) . Although changes in FACT-An Total Fatigue subscale ( Fatigue subscale ) scores were similar for the three dosage groups , there was a statistically significant correlation ( r = 0.435 , P < 0.001 ) between the change in hemoglobin levels and the change in Fatigue subscale scores . The proportion of transfused patients was significantly smaller in the 36 000 IU group compared with that in the 9000 IU group ( P = 0.022 , not adjusted for pre- study transfusions ) . The incidence of adverse events was similar in the three dosage groups . CONCLUSIONS Once-weekly epoetin-beta 36,000 IU for 12 weeks was well tolerated and significantly increased hemoglobin levels in anemic cancer patients receiving chemotherapy 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 Congestive heart failure ( CHF ) as a common comorbidity in patients with lung cancer , especially those of old age . The tumor combined with heart failure makes the reasons of dyspnea more complicated and effective drugs to improve symptoms are urgently needed . Recombinant human B-type natriuretic peptide ( rhBNP ) is a member of the natriuretic peptide family that exerts cardiovascular effects . The major goal of this study was to study the effect of rhBNP on patients with decompensated heart failure coexisted with lung cancer . Emergency decompensated HF patients with lung cancer admitted for dyspnea were r and omly assigned to open label therapy with st and ard treatment ( control group ) or st and ard treatment + rhBNP(rhBNP group ) for up to 7 days . Then we recorded the changes of symptoms , examined and followed up every 3 months to evaluate the effect of rhBNP on decompensated heart failure patients with lung cancer . We found that dyspnea , fatigue and edema of lower extremity were significantly improved in the rhBNP group compared to the control group after 7 days of treatment . Survival rate was not significantly different in the mean 18.4 + /- 8.6 months of follow-up . Results from our study suggested that rhBNP significantly improved symptoms in emergency decompensated HF patients with lung cancer admitted for dyspnea in the short-term , but did not improve survival rate in the long-term OBJECTIVE Cancer-related fatigue ( CRF ) is a common and one of the most important issues in palliative medicine , and it has been demonstrated to have a significant impact on patient quality of life ( QoL ) . The present pilot r and omized controlled study evaluated the efficacy and toxicity of methylprednisolone ( MP ) for CRF in advanced cancer patients . METHOD Our study was planned as a r and omized , double-blind , multicenter , placebo-controlled trial . Patients were r and omly assigned to an MP group , who received 32 mg/day of MP orally for 7 days , and a placebo group . The primary endpoint was an improvement in visual analog scale ( VAS ) score for fatigue from baseline to day 7 . The secondary endpoints were improvements in appetite loss and QoL as well as evaluating the safety of corticosteroids as palliative therapy . RESULTS It was not possible to complete patient registration . In total , 35 patients were r and omly assigned to an MP group ( n = 18 ) and a placebo group ( n = 17 ) . The mean changes in VAS score for fatigue were -9.06 in the placebo group and -1.56 in the MP group , and for appetite loss -6.44 in the placebo group and -8.06 in the MP group . In addition , there was no evidence that methylprednisolone improved appetite loss or QoL compared to placebo . The incidence of adverse effects was not greater in the MP group . Significant of Result : We conclude that our sample size was too small to prove the efficacy of methylprednisolone in improving fatigue . Our results were reported as a pilot study performed to support a subsequent larger trial CONTEXT One potential agent to improve symptoms and quality of life ( QoL ) in advanced cancer patients is adenosine 5'-triphosphate ( ATP ) . Several reports suggest that ATP may positively affect QoL and survival in patients with advanced non-small-cell lung cancer . OBJECTIVES To investigate the effects of ATP infusions on QoL parameters in patients with preterminal cancer of mixed tumor types . METHODS Ninety-nine preterminal cancer patients were r and omly allocated to receive either ATP intravenously weekly ( 8 - 10 hours/week , with maximum 50 μg/kg.minute ) for eight weeks or receive no ATP ( control group ) . QoL parameters were assessed until eight weeks and analyzed by repeated- measures analysis of covariance . RESULTS Fifty-one patients were r and omized to the ATP group and 48 to the control group . Unexpectedly , in the untreated control group , most of the outcome parameters did not deteriorate but remained stable or even significantly improved over time . Between the ATP and control groups , no statistically significant differences were observed for the large majority of outcome parameters , except for the strength of elbow flexor muscles in favor of the control group . CONCLUSION ATP infusions , at the dose and schedule studied , did not have a significant effect on QoL , functional status , or fatigue in preterminal cancer patients of mixed tumor types Background : The management of cancer-related anorexia/cachexia syndrome ( CACS ) is a great challenge in clinical practice . To date , practice guidelines for the prevention and treatment of CACS are lacking . The authors conducted a r and omized study to confirm the effectiveness and safety of treatment of CACS utilizing megestrol acetate ( MA ) plus thalidomide . Methods : One hundred and two c and i date s with CACS were r and omly assigned to two treatment groups ( trial group and control group ) : the trial group received MA ( 160 mg po , bid ) plus thalidomide ( 50 mg po , bid ) , while the control group received MA ( 160 mg po , bid ) alone . Treatment duration was 8 weeks . Results : Analysis of the trial group demonstrated a significant increase from baseline in body weight ( < 0.01 ) , quality of life ( p = 0.02 ) , appetite ( p = 0.01 ) , and grip strength ( p = 0.01 ) , and a significant decrease in fatigue , Glasgow Prognostic Score ( p = 0.05 ) , Eastern Cooperative Oncology Group performance status ( p = 0.03 ) , IL-6 ( p < 0.01 ) , and tumor necrosis factor-α ( p = 0.02 ) . In contrast , in the control group , endpoints with a significant improvement from baseline included body weight ( p < 0.02 ) and appetite ( p = 0.02 ) . The mean changes in the endpoints from baseline in the trial group were significantly greater compared with the control group : in the primary endpoints , body weight ( p = 0.05 ) , fatigue ( p < 0.01 ) and quality of life ( p = 0.01 ) , and in the secondary endpoints , grip strength ( p = 0.05 ) , Glasgow Prognostic Score ( p = 0.02 ) , Eastern Cooperative Oncology Group performance status ( p = 0.02 ) , IL-6 ( p < 0.01 ) and tumor necrosis factor-α ( p = 0.01 ) . Toxicity was found to be relatively negligible in both groups . Conclusion : A combination regimen of MA and thalidomide is more effective than MA alone in the treatment of CACS Background One of the modalities of treatment for breast cancer surgery pain is opioids , and opioids are associated with adverse effects such as itching and postoperative nausea and vomiting ( PONV ) . Intravenous ( IV ) lidocaine has been shown to reduce opioid consumption and to improve overall postoperative outcomes in abdominal surgery . In this study , we tested the effect of intraoperative IV lidocaine infusion on the quality of postoperative recovery after breast cancer surgery . Methods Seventy-one patients undergoing breast cancer surgery were r and omly assigned to receive either placebo ( group P ; n = 34 ) or IV lidocaine ( group L ; n = 37 , bolus 1.5 mg/kg at induction , then infusion at 2 mg/kg/h , stopped 2 hours after the end of surgery ) in a prospect i ve double-blind design . Intraoperative and postoperative morphine consumption was calculated . Postoperative pain scores , PONV , and fatigue were assessed at 2 , 24 , and 48 hours after surgery . Duration of postoperative hospital stay was recorded . Results Demographics were the same between the groups . There was no statistically significant difference in intraoperative or postoperative morphine consumption ( P = 0.188 and P = 0.758 ) between groups . Overall pain scores either at rest or activity ( P = 0.348 and P = 0.810 , respectively ) , PONV ( P = 0.350 ) , fatigue ( P = 0.758 ) , or duration of postoperative hospital stay ( P = 0.218 ) were not statistically different . Conclusions Our findings did not show a significant effect of IV lidocaine during breast cancer surgery on opioid consumption , pain score , PONV , or fatigue , indicating that the benefit of this approach does not generalize across all types of surgery Purpose Patients with malignancy sometimes develop painful mucositis and require patient-controlled analgesia ( PCA )  to treat their pain . Pain disrupts sleep and there is some evidence that analgesic medications also disrupt sleep . This study examined whether treatment with the sedative hypnotic eszopiclone could improve self-reports of sleep , fatigue , and pain as well as decrease opioid self-administered via PCA . Methods In patients who developed mucositis severe enough to require PCA treatment were r and omized double-blind to a 2-day trial on  eszopiclone or placebo-administered at bedtime . Patients completed question naires which assessed sleep , pain , and fatigue .  PCA medication was calculated in terms of morphine equivalents . Data were analyzed with unpaired t tests and repeated measures analysis of variance . Results Twenty-two patients were r and omized to placebo  and 23 to  eszopiclone .  Groups were comparable in age and treatment characteristics .  Mean pain scores were lower in the eszopiclone group at all time points ( morning p = 0.01 , afternoon p = 0.04 , evening p = 0.04 ) . The eszopiclone group reported increased sleep time ( p < 0.05 ) , fewer nighttime awakenings ( p < 0.001 ) , better self-reported sleep quality ( p = 0.01 ) , and depth ( p = 0.04 ) . There were no significant differences between eszopiclone and placebo in terms of self-reports of fatigue or opioid usage . ConclusionS edative hypnotic agents improve sleep and analgesia even in the setting of considerable pain and discomfort The fatigue prevalence in breast cancer survivors is high during the endocrine treatment . However , there are few evidence -based interventions to manage this symptom . The aim of this study was to investigate the effectiveness of spore powder of Ganoderma lucidum for cancer-related fatigue in breast cancer patients undergoing endocrine therapy . Spore powder of Ganoderma lucidum is a kind of Basidiomycete which is a widely used traditional medicine in China . 48 breast cancer patients with cancer-related fatigue undergoing endocrine therapy  were r and omized into the experimental or control group . FACT-F , HADS , and EORTC QLQ-C30 question naires data were collected at baseline and 4 weeks after treatment . The concentrations of TNF-α , IL-6 , and liver-kidney functions were measured before and after intervention . The experimental group showed statistically significant improvements in the domains of physical well-being and fatigue subscale after intervention . These patients also reported less anxiety and depression and better quality of life . Immune markers of CRF were significantly lower and no serious adverse effects occurred during the study . This pilot study suggests that spore powder of Ganoderma lucidum may have beneficial effects on cancer-related fatigue and quality of life in breast cancer patients undergoing endocrine therapy without any significant adverse effect This study evaluated the effects of epoetin alfa on patient-reported outcomes in patients with breast cancer receiving myelotoxic chemotherapy . Early intervention with epoetin alfa was well tolerated and improved anemia-related patient-reported outcomes CONTEXT Fatigue is highly prevalent in population s with advanced illness and is often associated with depressed mood . The role of psychostimulant therapy in the treatment of these conditions remains ill defined . OBJECTIVES To evaluate the response of fatigue and depression in patients with advanced illness to titrated doses of methylpheni date ( MP ) as compared with placebo . METHODS In a r and omized , double-blind , placebo-controlled trial , 30 hospice patients , both in patients and out patients , who had fatigue scores of at least four on a scale of zero to 10 ( 0=no fatigue and 10=worst fatigue ) , were r and omly assigned to receive either 5 mg of MP at 8 am and 1 pm or placebo . Doses of MP were titrated every three days according to response and adverse effects . Home care patients were monitored daily by telephone and visited by a research nurse on Study Days 0 ( baseline ) , 3 , 7 , and 14 . Fatigue was assessed using the Piper Fatigue Scale as the primary outcome measure and vali date d by the Visual Analogue Scale for Fatigue and the Edmonton Symptom Assessment Scale ( ESAS ) fatigue score .  Subjects in inpatient facilities were interviewed or assessed by staff on an identical schedule . Depressive symptoms were assessed by the Beck Depression Inventory-II , Center for Epidemiologic Studies Depression Scale , and the ESAS depression score . Primary statistical analysis was conducted using repeated- measures multivariate analysis of the variance . RESULTS Both MP- and placebo-treated groups had similar measures of fatigue at baseline . Patients taking MP were found to have significantly lower fatigue scores ( Piper Fatigue Scale , Visual Analogue Scale for Fatigue , and ESAS ) at Day 14 compared with baseline . The improvement in fatigue with MP treatment was dose-dependent ; the mean average effective dose was 10 mg on Day 3 and 20 mg on Day 14 ( dose range of 10 - 40 mg ) . Placebo-treated individuals showed no significant improvement in fatigue . For patients with clinical ly significant depression on Day 0 , treatment with MP was associated with a significant reduction in all test indices for depressed mood . For the placebo group , the changes in measures of depression were less than observed in the treatment group but were inconsistent between assessment tools . No significant toxicities were observed . CONCLUSION MP reduced symptoms of fatigue and depression when compared with placebo . The effect of MP on fatigue was dose-dependent and sustained over the duration of the study Background Breast cancer is the most common cancer amongst Malaysian women . Both the disease and its treatment can disrupt the lives of the woman and adversely affect all aspects of life and thus can alter a woman ’s quality of life . The aim of this study was to examine the effect of virgin coconut oil ( VCO ) on the quality of life ( QOL ) of patients diagnosed with breast cancer . Methods This was a prospect i ve study of breast cancer patients admitted into the Oncology Unit of Hospital Universiti Sains Malaysia , Kubang Kerian , Kelantan , Malaysia . The sample consisted of 60 patients with stage III and IV breast cancer allocated to either an intervention group ( n = 30 ) or a control group ( n = 30 ) using a simple r and om table . QOL was evaluated from the first cycle of chemotherapy to the sixth cycle , and data were collected using a vali date d Bahasa Malaysia version of the European Organization for Research and Treatment of Cancer Quality of Life Question naire Breast Cancer Module ( EORTC QLQ-C30 ) and its breast-specific module ( QLQ-BR 23 ) . Results The mean age of breast cancer patients was 50.2 ( SD = 13.5 ) years . There were significant mean score differences for functioning and global QOL between groups ( α < 0.01 ) . The intervention group also had better scores for symptoms including fatigue , dyspnea , sleep difficulties , and loss of appetite compared to the control group . Although there are deteriorations for sexual enjoyment , the intervention group exhibited improvement in breast functioning and symptom scores for body image , sexual function , future perspective , breast symptoms , and systemic therapy side effects . Conclusion VCO consumption during chemotherapy helped improve the functional status and global QOL of breast cancer patients . In addition , it reduced the symptoms related to side effects of chemotherapy Study Objective A safe alternative to erythropoiesis‐stimulating agents to treat anemia is warranted in patients with cancer and anemia ; thus the objective of this trial was to compare the efficacy and safety of intravenous ( IV ) iron isomaltoside with oral iron in patients with cancer and anemia by testing the noninferiority of IV versus oral iron . Design Phase III , prospect i ve , open‐label , comparative , r and omized , noninferiority , multicenter trial . Setting Forty‐seven hospitals or private cancer clinics in Asia , the United States , and Europe . Patients A total of 350 patients with cancer and anemia . Intervention Patients were r and omized in a 2:1 ratio to either intravenous iron isomaltoside or oral iron sulfate . Patients in the iron isomaltoside group were then r and omized into an infusion subgroup ( single intravenous infusions of a maximum dose of 1000 mg over 15 min ) or a bolus injection subgroup ( bolus injections of 500 mg over 2 min ) . Measurements and Main Results The primary efficacy outcome was change in hemoglobin concentration from baseline to week 4 . Changes in other relevant hematology variables , effect on quality of life , and safety outcomes were also assessed . The primary efficacy outcome was tested for noninferiority , whereas the remaining outcomes were tested for superiority . Iron isomaltoside was noninferior to oral iron in change in hemoglobin concentration from baseline to week 4 ( difference estimate 0.016 , 95 % confidence interval –0.26 to 0.29 , p<0.001 ) . A faster onset of the hemoglobin response was observed with infusion of iron isomaltoside ( superiority test : p=0.03 at week 1 ) , and a sustained effect on hemoglobin level was shown in both the iron isomaltoside and oral iron treatment groups until week 24 . A significant mean decrease in fatigue score was observed from baseline to week 12 in the iron isomaltoside group ( p<0.001 ) but not in the oral iron group ( p=0.057 ) . A higher proportion of patients treated with oral iron  experienced adverse drug reactions ( 18.8 % vs 6.6 % , p<0.001 ) and discontinued the trial due to intolerance ( 8.0 % vs 0.9 % , p=0.001 ) . Transient hypophosphatemia ( phosphate level less than 2 mg/dl ) was reported at similar low frequencies among the groups : 7.1 % in the iron isomaltoside infusion subgroup versus 8.5 % in the iron isomaltoside bolus injection subgroup versus 5.4 % in the oral iron group . Conclusion This trial demonstrated comparable sustained increases in hemoglobin concentration over time with both iron isomaltoside and oral iron . Iron isomaltoside was better tolerated than oral iron , and fatigue was significantly decreased with iron isomaltoside . Low rates of clinical ly insignificant hypophosphatemia were reported in patients receiving both treatments 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 Impaired cognition , fatigue , and diminished quality of life ( QOL ) are commonly associated with breast cancer chemotherapy . This r and omized , double-blind , placebo-controlled pilot trial assessed the feasibility of quantifying the effects of epoetin alfa on cognitive function and mood , and evaluated its effects on fatigue and QOL in patients with breast cancer treated with anthracycline-based adjuvant or neoadjuvant chemotherapy . Patients were r and omized to receive epoetin alfa 40,000 U subcutaneously once weekly or  placebo at the beginning of 4 cycles of chemotherapy  administered over 12 weeks . Cognitive function was assessed by Executive Interview ( EXIT25 ) and Clock Drawing Tasks ;  mood by Profile of Mood States ; anemia-related symptoms , including fatigue , by the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) subscale ; and QOL by Linear Analog Scale Assessment . Ninety-four patients were evaluable for efficacy and safety . Mean change in EXIT25 scores from baseline to cycle 4 in the epoetin alfa group was 1.3 + /- 3.3 ; the mean change was 0.3 + /- 2.4 in the placebo group ( a negative change indicates improved executive function ) . There was no difference between groups in mean change in EXIT25 score from baseline to 6-month follow-up assessment . Mean hemoglobin levels were higher in the  epoetin alfa  group compared with the placebo group after 4 cycles of chemotherapy . Epoetin alfa recipients had less of a decrease in FACT-An subscale scores from baseline to cycle 4 and improvement in FACT-An subscale scores at 6-month follow-up assessment compared with placebo . Epoetin alfa therapy was well tolerated . These data suggest that epoetin alfa may have attenuated the cognitive impairment and fatigue that occurred during adjuvant breast cancer chemotherapy Nutritional effects have traditionally focused on outcomes , such as nitrogen balance , wound healing , or muscle strength . Little emphasis has been placed on how biochemical or physical improvements translate into functional changes as perceived by the patient . Because glutamine (GLN)-supplemented nutrition promotes protein synthesis and improves nitrogen balance , we assessed the mood of individuals participating in a r and omized controlled blinded trial receiving GLN solutions . Patients ( n = 23 ) undergoing marrow transplantation were r and omized by the research pharmacist to receive either st and ard total parenteral nutrition ( TPN ) ( control ) or GLN-containing TPN ( 40 g of glutamine total ) . The solutions were isocaloric and isonitrogenous and were administered until the patient was eating 50 % of estimated requirements . Before TPN and on admission to the hospital , the patient completed the Profile of Mood States question naire , a st and ardized test quantifying the degree of tension , depression , anger , vigor , fatigue , and confusion . The patient completed the question naire again at the end of TPN near discharge . The tests were scored and the change from baseline for each mood for both groups of patients was calculated at the completion of TPN . The scores for vigor in the control group ( delta scores ) decreased over the course of hospitalization as would be expected with a serious illness . The group receiving glutamine TPN , however , essentially showed little change in vigor from baseline and the delta score was significantly different from the control group ( delta vigor score -0.85 + /- 2.1 in the glutamine group vs. -5.90 + /- 1.7 in the control group ; p = .07 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To study whether perioperative treatment with darbepoetin alfa ( DA ) improves physical performance following colorectal cancer surgery . Methods : Patients admitted for planned colorectal cancer surgery were r and omized to receive either weekly placebo or DA 300 or 150 µg depending on the hemoglobin ( Hb ) concentration . Patients were assessed 10 days before , as well as 7 and 30 days after surgery for work capacity , postural sway , muscle strength , fatigue and quality of life ( QoL ) . The primary outcome measure were the changes in patients ’ physical performance from preoperative to postoperative day 7 . Results : Of 221 included patients , 151 were evaluable . Baseline characteristics were similar in the 2 groups . Patients receiving DA had a significantly better working capacity on day 7 ( p = 0.03 ) and day 30 ( p = 0.03 ) compared with the placebo group . There were no statistically significant differences between the 2 groups on days 7 or 30 for fatigue , postural sway and QoL.  DA treatment significantly ( p < 0.01 ) reduced the decrease in Hb concentrations on day 7 and result ed in an earlier return ( p < 0.01 ) to the preoperative Hb concentration compared to placebo treatment . Conclusion : Perioperative DA  treatment improved postoperative work capacity and Hb concentrations , but had no effect on postoperative fatigue , postural sway , QoL and muscle strength This study evaluated the efficacy of olanzapine in preventing chemotherapy-induced nausea and vomiting ( CINV ) and improving the quality of life ( QoL ) of patients with cancer during chemotherapy . Two hundred twenty-nine patients with cancer who received chemotherapy from January 2008 to August 2008 were enrolled , and they were r and omised to receive olanzapine or a 5-HT3 receptor antagonist . The patients completed a CINV question naire once daily on days 1 - 5 and a QoL question naire on days 0 and 6 . The complete response ( CR ) rates for nausea ( 76.85 % versus 46.2 % ) and vomiting ( 84.3 % versus 67.6 % ) were significantly higher in the olanzapine group than in the 5-HT3 receptor antagonist group for delayed CINV but not for acute CINV . The CR rates for nausea ( 76.85 % versus 44.44 % ) and vomiting ( 85.95 % versus 67.59 % ) were also significantly higher in the olanzapine group for the 5 days post-chemotherapy . After chemotherapy , global health status , emotional functioning , and insomnia were improved in the olanzapine group but worsened in the 5-HT3 receptor antagonist group , whereas cognitive functioning and appetite loss were unchanged . Moreover , olanzapine significantly improved global health status , emotional functioning , social functioning , fatigue , nausea/vomiting , insomnia , and appetite loss .  Olanzapine improved the QoL of patients with cancer during chemotherapy , in part by reducing the incidence of delayed CINV Anaemia is common in patients receiving chemotherapy , causing symptoms that have a major impact on quality of life ( QoL ) . Epoetin beta rapidly increases haemoglobin ( Hb ) levels and improves QoL in anaemic patients with a variety of tumours . This was a r and omized , double-blind , parallel-group , dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumours receiving chemotherapy . Adult patients with anaemia ( Hb < 11 g/dL ) were r and omized to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12 weeks . All patients received oral iron supplementation .  Haemoglobin levels , transfusion need and QoL [ Functional Assessment of Cancer Therapy-fatigue ( FACT-F ) subscale score ] were assessed at regular intervals . Fifty patients were r and omized ; 30 patients received epoetin beta 30,000 IU once weekly and 20 received 20,000 IU once weekly . Mean ( + /- SD ) increase in Hb from baseline to week 12 was 1.75 + /- 2.15 g/dL in the 30,000 IU group ( P = 0.008 vs. baseline ) and 1.04 + /- 1.75 g/dL in the 20,000 IU group ( non-significant ) . Haemoglobin response ( increase in Hb > or=2 g/dL from baseline ) was observed in 78.3 % of patients receiving epoetin beta 30,000 IU and 66.7 % receiving epoetin beta 20,000 IU . Improvements in FACT-F subscale score were significantly ( P < 0.001 ) correlated with increases in Hb level . Transfusion use was low during the study in both groups . Both epoetin beta regiments were well tolerated and there were no dose-dependent adverse events .  Epoetin beta 30,000 IU once weekly is an effective and well-tolerated treatment of anaemia in patients with solid tumours 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 CONTEXT Opioid therapy often shows insufficient efficacy and substantial adverse events in patients with advanced cancer . OBJECTIVES To assess the efficacy of caffeine infusion as an adjuvant analgesic to opioid therapy in patients with advanced cancer . METHODS A double-blind , r and omized , placebo-controlled trial was conducted in the palliative care wards of two teaching hospitals in South Korea . A total of 20 of 41 participants were assigned to the caffeine group and 21 to the placebo group . The participants received caffeine ( 200 mg ) or normal saline intravenously once a day for two days . The primary outcome was pain , which was measured using a 10-point rating scale . Other outcomes included drowsiness , confusion , nausea , sleep disturbance , fatigue , and sadness . RESULTS Three participants ( two in the caffeine group and one in the placebo group ) dropped out after the first intervention because of insomnia ; thus , 38 participants completed the trial .  Pain score was significantly lower in the caffeine group than in the placebo group after the second trial ( P=0.038 ) . The mean reduction in pain intensity in the caffeine group was 0.833 ( 95 % confidence interval [ CI ] 0.601 - 1.066 ) , whereas that in the placebo group was 0.350 ( 95 % CI 0.168 - 0.532 ) . Considering an improvement higher than 30 % from baseline as the threshold value , drowsiness improved significantly in the caffeine group after the first trial ( P=0.041 ) . Adverse event rate did not differ between the two groups . CONCLUSION Caffeine infusion significantly reduced pain and drowsiness , but the reduction did not reach clinical significance in patients with advanced cancer undergoing opioid therapy . Further investigations are warranted PURPOSE Fatigue and depression typically occur together in cancer patients , suggesting a common etiology , perhaps based on serotonin . This r and omized clinical trial tested whether paroxetine , a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin , would reduce fatigue in cancer patients and whether any reduction was related to depression . PATIENTS AND METHODS Cancer patients undergoing chemotherapy for the first time were assessed for fatigue .  Of 704 patients who reported fatigue at their second chemotherapy cycle , 549 patients were r and omly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks . The assessment s of fatigue and depression were performed at cycles 3 and 4 of chemotherapy . RESULTS A total of 244 patients treated with paroxetine and 235 patients treated with placebo  provided assessable data . No difference was detected in fatigue between patient groups . At the end of the study , there was a difference between groups in the mean level of depression ( Center for Epidemiologic Studies Depression scores , 12.0 v 14.8 , respectively ; P < .01 ) . CONCLUSION Paroxetine had no influence on fatigue in patients receiving chemotherapy .  A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels The objective of this r and omised , multicentre , double-blind clinical trial was to investigate the impact of PS76A2 , an aqueous mistletoe extract st and ardised to mistletoe lectins , on quality of life ( QoL ) in breast cancer patients . A total of 352 patients were r and omly allocated to 2 groups receiving PS76A2 ( 15 ng mistletoe lectin/0.5 ml ) or matching placebo twice weekly for 4 to 6 cycles of CMF ( cyclophosphamide , methotrexate , fluorouracil ) chemotherapy followed by 2 months follow-up . The primary efficacy end-point was the change from baseline of 3 FACT-G subscales ( physical , emotional and functional well-being ) during the fourth CMF cycle . Secondary measures included GLQ-8 ( 8 linear analogue self- assessment scales ) , Spitzer 's uniscale and haematological variables . The main variables of safety analysis were adverse events , including injection site reactions and clinical laboratory tests . The results showed that physical , emotional and functional well-being improved upon PS76A2 , but deteriorated following placebo . The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G , which was analysed as O'Brien 's rank sum of its 3 subscales : The total score increased by 4.40 + /- 11.28 , indicating a higher QoL after PS76A2 , but decreased by 5.11 + /- 11.77 with placebo ( p<0.0001 ) . The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 ( sum of item nos. 1 , 5 , 6 , 7 , 8) and GLQ-3 ( sum of item nos. 2 , 3 , 4 ) . GLQ-5 characterises typical aspects of QoL , while GLQ-3 consists of 3 side-effects of CMF ( feeling sick , numbness or pins and needles , loss of hair ) . GLQ-5 decreased by 42.9 + /- 125.0 upon PS76A2 , indicating an improvement in QoL , but increased by 60.3 + /- 94.0 upon placebo ( p<0.0001 ) . GLQ-3 deteriorated in both groups ( PS76A2 : 13.9 + /- 52.4 ; placebo : 34.5 + /- 57.0 ) , but the differences in favour of PS76A2 were , nevertheless , statistically significant ( p=0.0007 ) . The total score GLQ-8 improved by 28.9 + /- 154.6 after PS76A2 and deteriorated by 94.8 + /- 141.1 after placebo ( p<0.0001 ) . Spitzer 's uniscale improved by 12.2 + /- 30.7 upon PS76A2 and deteriorated by 10.8 + /- 26.1 with placebo ( p<0.0001 ) . After follow-up without chemotherapy , a significant treatment difference in favour of PS76A2 was determined by means of FACT-G , GLQ-8 and Spitzer 's uniscale . PS76A2 was well tolerated in this trial , with the exception of slight local reactions in 17.6 % of the PS76A2 group . In conclusion , PS76A2 ( 15 ng mistletoe lectin/0.5 ml twice weekly ) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up This r and omized , controlled trial evaluated the effect of darbepoetin alfa on hospitalization days , transfusion requirements , hemoglobin levels , and fatigue in patients with anemia of cancer ( AOC ) . Eligible patients were anemic ( hemoglobin < or=11 g/dl ) due to cancer , > or=18 years old , and had not received chemotherapy or radiotherapy within 4 weeks of study screening . Patients were r and omized 4:1 to receive darbepoetin alfa , 3.0 microg/kg every 2 weeks ( Q2W ) ( n = 226 ) , or observation only for 12 weeks ( n = 59 ) , followed by an optional 9 weeks of darbepoetin alfa , 3.0 microg/kg Q2W . Endpoints were compared between the two treatment arms at week 13 . A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect , so the study was terminated early . Therefore , results for the primary endpoint should be interpreted cautiously . The hospitalization rate was similar ( 0.5 days ) for both the darbepoetin alfa and observation groups ( p = .73 ) . Transfusion incidence ( weeks 5 - 12 ) was significantly lower for darbepoetin alfa patients ( 8 % ) than for observation patients ( 22 % ) ( p = .0092 ) . By week 13 , hemoglobin increased by 2.1 g/dl in patients receiving darbepoetin alfa , compared with 0.1 g/dl in the observation group p < .0001 . Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy-Fatigue score ( mean change in score at week 13 : darbepoetin alfa , 6.0 ; observation , 2.2 ; p < .05 ) . Darbepoetin alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC , result ing in significant improvements in health-related quality of life ABSTRACT Purpose : Paullinia cupana ( guaraná ) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue ( CRF ) in patients with breast cancer . We aim ed to evaluate the efficacy of a purified dry extract of P. cupana ( PC-18 ) in patients with various solid tumors treated with chemotherapy . Methods : We included 40 patients with solid tumors who showed increases in their Brief Fatigue Inventory ( BFI ) question naire scores after 1 week of systemic chemotherapy . PC-18 was administered at 37.5 mg by mouth two times per day ( PO bid ) , starting after 1 week of chemotherapy , for 3 weeks ( induction phase ) . Patients who had an improvement in or stabilization of their BFI scores were r and omized to receive either PC-18 at the same dose or placebo for the following 3 weeks ( maintenance phase ) . Results : After PC-18 treatment , the BFI fatigue scores improved or stabilized in 36 out of the 40 patients ( mean BFI score difference = 2.503 ; 95 % confidence interval : 1.716–3.375 , p = .0002 ) . Three weeks after r and omization ( 16 patients on PC-18 and 17 on placebo ) , we observed no significant differences in the BFI , Functional Assessment of Chronic Illness Therapy , Hospital Anxiety and Depression Scale , and Pittsburgh Sleep Quality Index scores between patients r and omized to PC-18 versus placebo . Conclusions : We conclude that the PC-18 extract may be effective for the treatment of CRF in patients with a variety of solid tumors . A conditioning effect , which was observed in patients who had a beneficial effect of PC-18 on CRF , may explain the better than expected fatigue scores of the placebo-treated patients BACKGROUND Patients receiving chemotherapy often develop anemia .  Darbepoetin alfa ( Aranesp(TM ) ) is an erythropoiesis-stimulating glycoprotein that has been shown , in dose-finding studies , to be safe and clinical ly active when administered to patients with cancer every 1 , 2 , or 3 weeks . This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy . METHODS In this multicenter , double-blind , placebo-controlled study , 320 anemic patients ( hemoglobin < or=11.0 g/dL ) were r and omly assigned to receive darbepoetin alfa or placebo injections weekly for 12 weeks . The 297 patients who completed at least the first 28 days of study were assessed for  red blood cell transfusions  , the primary endpoint . Patients were also assessed for hemoglobin concentration ( i.e. , hematopoietic response ) , adverse events , antibody formation to darbepoetin alfa , hospitalizations , Functional Assessment of Cancer Therapy (FACT)-Fatigue score , and disease outcome . Efficacy endpoints were assessed using Kaplan-Meier analyses , Cox proportional hazards analyses , and chi-square tests where appropriate . All statistical tests were two-sided . RESULTS Patients receiving darbepoetin alfa required fewer transfusions ( 27 % versus 52 % ; mean difference = 25 % ; 95 % confidence interval [ CI ] = 14 % to 36 % ; P<.001 ) , required fewer units of blood ( 0.67 versus 1.92 ; mean difference = 1.25 , 95 % CI = 0.65 to 1.84 ; P<.001 ) , had more hematopoietic responses ( 66 % versus 24 % ; mean difference = 42 % ; 95 % CI = 31 % to 53 % ; P<.001 ) , and had better improvement in FACT-Fatigue scores ( 56 % versus 44 % overall improvement ; 32 % versus 19 % with > or=25 % improvement ; mean difference = 13 % ; 95 % CI = 2 % to 23 % , P = .019 ) than patients receiving placebo . Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug . Adverse events were similar between the groups . CONCLUSIONS Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy . Darbepoetin alfa decreased blood transfusion requirements , increased hemoglobin concentration , and decreased fatigue . Although no conclusions can be drawn about survival from this study , the potential salutary effect on disease outcome warrants further investigation in a prospect ively design ed study Objective To evaluate the impact of Jinlongshe Granule ( 金龙蛇颗粒 , JLSG ) on quality of life ( QOL ) of stage IV gastric cancer patients . Methods This r and omized , double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer . They were equally r and omized into a JLSG group and a placebo group . Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine ( CM ) treatment based on syndrome differentiation . Patients in JLSG group received additional JLSG , and those in the placebo group received an additional placebo .  In the JLSG group , 19 patients who completed the study were used for analysis . In the placebo group , finally the data of 20 patients who completed the study were used for analysis . The treatment course was at least 3 months , and the follow-up duration was at least 6 months in 5 interviews . Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Question naire C30 ( EORTC QLQ-C30 ) obtained at the 5 interviews were compared using different patient groups , changes over time and changes within one group over time independently to observe the tendency of changes in the scores . Results Using time as the variant , there was signifificant difference in 4 functional scales ( physical , role , emotional and social , P<0.05 ) , 3 symptom scales ( fatigue , nausea and vomiting and pain , P<0.05 ) and a global health status/QOL scale ( P<0.05 ) and 6 single symptoms dyspnoea ( P>0.05 ) , insomnia ( P<0.05 ) , appetite loss ( P<0.05 ) , constipation ( P<0.05 ) , diarrhea ( P>0.05 ) and financial difficulties ( P<0.05 ) . There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants ( P<0.05 or P<0.01 ) . Conclusion Additional use of JLSG on the basis of routine CM treatment could improve the somatic function , role function , emotional function , social function , cognitive function and general QOL of patients with advanced gastric cancer , and relieve the symptoms of fatigue , nausea and vomiting , pain , loss of appetite and constipation Purpose Cancer-related fatigue ( CRF ) is one of the most common symptoms reported by cancer patients . This r and omized trial investigated the efficacy of the amino acid jelly Inner Power ® ( IP ) , a semi-solid , orally administrable dietary supplement containing coenzyme Q10 and l-carnitine , in controlling CRF in breast cancer patients in Japan . Methods Breast cancer patients with CRF undergoing chemotherapy were r and omly assigned to receive IP once daily or regular care for 21 days . The primary endpoint was the change in the worst level of fatigue during the past 24 h ( Brief Fatigue Inventory [ BFI ] item 3 score ) from day 1 ( baseline ) to day 22 . Secondary endpoints were change in global fatigue score ( GFS ; the average of all BFI items ) , anxiety and depression assessed by the Hospital Anxiety and Depression Scale ( HADS ) , quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Question naire Core 30 ( EORTC QLQ-C30 ) and EORTC Breast Cancer-Specific QLQ ( EORTC QLQ-BR23 ) , and adverse events . Results Fifty-nine patients were enrolled in the study , of whom 57 were included in the efficacy analysis . Median patient age was 50 years . Changes in the worst level of fatigue , GFS , and current feeling of fatigue were significantly different between the intervention and control groups , whereas the change in the average feeling of fatigue was not significantly different between groups . HADS , EORTC QLQ-C30 , and EORTC QLQ-BR23 scores were not significantly different between the two groups . No severe adverse events were observed . Conclusion IP may control moderate-severe CRF in breast cancer patients .Trial registration The registration number of this study in the University Hospital Medical Information Network Clinical Trials Registry ( UMIN-CTR ) is UMIN000008646 We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-α ( IFN-α ) therapy  can be reduced by pretreatment with the antidepressant , paroxetine . Using dimensional analyses , the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-α therapy .  Forty patients with malignant melanoma eligible for IFN-α treatment  were r and omly assigned to receive either paroxetine or placebo in a double-blind design . Neuropsychiatric assessment s were conducted at regular intervals during the first twelve weeks of IFN-α therapy and included the 21-item Hamilton Depression Rating Scale , the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale . Neurovegetative and somatic symptoms including anorexia , fatigue and pain appeared within two weeks of IFN-α therapy in a large proportion of patients . In contrast , symptoms of depressed mood , anxiety and cognitive dysfunction appeared later during IFN-α treatment and more specifically in patients who met DSM-IV criteria for major depression . Symptoms of depression , anxiety , cognitive dysfunction and pain were more responsive , whereas symptoms of fatigue and anorexia were less responsive , to paroxetine treatment . These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-α , and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced “ sickness behavior . OBJECTIVE This is the first clinical trial for Japanese to evaluate the dose-response and determine the clinical ly effective dose of darbepoetin alpha by weekly subcutaneously administration in anemic patients with lung cancer or ovarian cancer receiving chemotherapy . METHODS Eligible patients were required to have anemia ( hemoglobin level of < or=11.0 g/dl ) . Patients were r and omized in a 1:1:1 ratio to receive darbepoetin alpha ( 1.0 , 2.25 or 4.5 microg/kg ) subcutaneously once a week for up to 12 weeks . The study drug was withheld from patients who had a hemoglobin level > 15.0 g/dl ( for men ) or 14.0 g/dl ( for women ) , and reinstated at 50 % of the previous weekly dose when the hemoglobin level decreased to < or=13.0 g/dl . Quality -of-life assessment s were conducted using the Japanese version of the Functional Assessment of Cancer Therapy-anemia ( FACT-an ) question naire . RESULTS Hemoglobin response rate was 31.6 % , 55.6 % and 70.3 % in 1.0 , 2.25 and 4.5 microg/kg groups , respectively . The dosages of 2.25 and 4.5 microg/kg thus met the clinical ly effective dose criterion of at least 50 % of patients achieving a hemoglobin response . The FACT-fatigue subscale had a high internal consistency with Cronbach 's alpha score . Although no improvement in FACT-fatigue subscale score from baseline to the end of the treatment phase was confirmed for any dose group , there was a correlation between FACT-fatigue subscale score and hemoglobin concentration .  Darbepoetin alpha appears to be well tolerated in this setting and no dose-dependent adverse events were observed . CONCLUSIONS Darbepoetin alpha alleviated anemia caused by platinum-based chemotherapy , and the dosage of 2.25 microg/kg was the lowest dose that met the clinical ly effective dose criteria when administered once weekly PURPOSE This r and omized , double-blind , placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements , hematopoietic parameters , quality of life ( QOL ) , and safety in anemic cancer patients receiving nonplatinum chemotherapy . The study also explored a possible relationship between increased hemoglobin and survival . PATIENTS AND METHODS Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL , or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy , were r and omized 2:1 to epoetin alfa  150 to 300 IU/kg ( n = 251 ) or placebo ( n = 124 ) three times per week subcutaneously for 12 to 24 weeks . The primary end point was proportion of patients transfused ; secondary end points were change in hemoglobin and QOL . The protocol was amended before unblinding to prospect ively collect and assess survival data 12 months after the last patient completed the study . RESULTS Epoetin alfa , compared with placebo , significantly decreased transfusion requirements ( P = .0057 ) and increased hemoglobin ( P < .001 ) . Improvement of all primary cancer- and anemia-specific QOL domains , including energy level , ability to do daily activities , and fatigue , was significantly ( P < .01 ) greater for epoetin alfa versus placebo patients . Although the study was not powered for survival as an end point , Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa ( P = .13 , log-rank test ) , and Cox regression analysis showed an estimated hazards ratio of 1.309 ( P = .052 ) favoring epoetin alfa .  Adverse events were comparable between groups . CONCLUSION Epoetin alfa safely and effectively ameliorates anemia and significantly improves  QOL  in cancer patients receiving nonplatinum chemotherapy . Encouraging results regarding increased survival warrant another trial design ed to confirm these findings Purpose Fatigue is a prevalent , distressing side effect of cancer and cancer treatment which commonly coexists with insomnia . Cognitive behavioral therapy for insomnia ( CBT-I ) has been shown to improve insomnia  in cancer patients , but less is known about its ability to impact fatigue . This work is the analysis for a secondary aim of a four-arm r and omized controlled trial ( RCT ) study assessing the combined and comparative effect of CBT-I and a wakefulness-promoting agent , armodafinil ( A ) , to improve sleep and daytime functioning in cancer survivors . Herein , we examine the effect of CBT-I , with and without A , on fatigue in cancer survivors . Patients and methods This study was a four-arm factorial study with CBTI-I ( yes/no ) versus A ( yes/no ) . It consisted of 96 cancer survivors ( average age 56 years ; 88 % female ; 68 % breast cancer ) .  Fatigue was assessed by the brief fatigue inventory ( BFI ) and the FACIT-Fatigue scale . The analysis assessed the additive effects of CBT-I and A and possible non-additive effects where the effect of CBT-I changes depending on the presence or absence of A. Results Analyses adjusting for baseline differences showed that CBT-I  improved fatigue as measured by two separate scales ( BFI : P = 0.002 , Std . error = 0.32 , effect size ( ES ) = 0.46 ; FACIT-Fatigue : P < 0.001 , Std . error = 1.74 , ES = 0.64 ) . Armodafinil alone did not show a statistically significant effect on fatigue levels ( all Ps > 0.40 ) nor did the drug influence the efficacy of CBT-I. Structural equation analysis revealed that reductions in insomnia severity were directly responsible for improving cancer-related fatigue . Conclusions CBT-I with and without armodafinil result ed in a clinical ly and statistically significant reduction of subjective daytime fatigue in cancer survivors with chronic insomnia . Armodafinil did not improve cancer-related fatigue ( CRF ) and did not change the efficacy of CBT-I. Patients reporting CRF should be screened and , if indicated , treated for insomnia as part of a comprehensive fatigue management program BACKGROUND Coenzyme Q10 ( CoQ10 ) is a common antioxidant supplement with known cardioprotective effects and potential anticancer benefits . OBJECTIVES We performed a r and omized , double-blind , placebo-controlled study of oral CoQ10 in female breast cancer patients with the primary objective of determining CoQ10 's effects on self-reported fatigue , depression , and quality of life ( QOL ) . Methods Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were r and omized to oral supplements of 300 mg CoQ10 or placebo , each combined with 300 IU vitamin E , divided into 3 daily doses . Treatment was continued for 24 weeks . Blood tests , QOL measures , and levels of plasma CoQ10 and vitamin E  were obtained at baseline and at 8 , 16 , and 24 weeks . Mixed-effects models were used to assess treatment differences in outcomes over time . RESULTS Between September 2004 and March 2009 , 236 women were enrolled . Treatment arms were well balanced with respect to age ( range , 28 - 85 years ) , pathologic stage ( stage 0 , 91 % ; stage 1 , 8 % ; stage II , 1 % ) , ethnicity ( white , 87 % ; black , 11 % ; Hispanic , 2 % ) , and planned therapy . Baseline CoQ10 levels in the CoQ10 and placebo arms were 0.70 and 0.73 microg/mL , respectively ; the 24-week  CoQ10 levels were 1.83 and 0.79 microg/mL , respectively . There were no significant differences between the CoQ10 and placebo arms at 24 weeks for scores on the Profile of Mood States-Fatigue question naire ( least squares means , 7.08 vs 8.24 , P = .257 ) , the Functional Assessment of Chronic Illness Therapy-Fatigue tool ( 37.6 vs 37.6 , P = .965 ) , the Functional Assessment of Cancer Therapy-Breast Cancer instrument ( 111.9 vs 110.4 , P = .577 ) , or the Center for Epidemiologic Studies -Depression scale ( 11.6 vs 12.3 , P = .632 ) . CONCLUSIONS Supplementation with conventional doses of CoQ10 led to sustained increases in plasma CoQ10 levels but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment 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 Patients with inoperable head and neck cancer were treated with a spleen peptide preparation ( Polyerga ) in a phase III r and omized , placebo-controlled double-blind study during chemotherapy ( cisplatin/carboplatin , 5-fluorouracil ) to investigate further the efficacy of this peptide preparation as supportive treatment under chemotherapy . Immunological changes as well as quality of life aspects were examined . Forty patients were included in this study . The peptide preparation had a significant stabilizing effect on the peripheral blood lymphocyte status during chemotherapy cycles ( Student t-test , p = 0.05 ) and tended to stabilize the shift of granulocyte count ( Student t-test , p = 0.18 ) . In addition , the group receiving the verum showed a remarkable stabilization of body weight ( Mann-Whitney U-test , p = 0.17 ) during chemotherapy treatment and the generally observed increase of fatigue-inertia during the chemotherapy cycles was significantly reduced ( Student t-test , p = 0.01 ) OBJECTIVE Erythropoietin is shown to be an effective treatment for anemia in various types of cancers , however only limited studies have evaluated its benefits in advanced hormone-refractory prostate cancer ( HRPC ) . This multi-center study investigated the influence of 2 different doses of epoetin beta on quality of life , hemoglobin level , need for blood transfusion , and safety , in the treatment of anemia in patients with metastatic HRPC . MATERIAL S AND METHODS This study r and omized 180 patients to receive either epoetin beta 1000 IU or 5000 IU subcutaneously 3 times per week for 12 weeks . Hemoglobin was evaluated at study start and 6 time-points during the study . Quality of life ( QoL ) was assessed by the European Organization for Research and Treatment of Cancer question naire , QLC-C30 , before treatment start and after 6 and 12 weeks of treatment . Best supportive care and blood transfusions were given , if clinical ly indicated . Additional laboratory values and adverse events were followed for safety . RESULTS Hemoglobin increased significantly ( > 20 g/l ) in 43 % in the high dose ( HD ) group and 25 % in the low dose ( LD ) group in response to treatment . Levels were significantly higher in the HD group than the LD group ( p < 0.001 ) after 8 and 12 weeks . QoL improved significantly if the increase in hemoglobin was > 20 g/l . Significantly more patients in the LD group received blood transfusions than the HD group ( p < 0.005 ) . There were no differences between the groups regarding overall quality of life and fatigue . The treatment was well tolerated in both groups . CONCLUSIONS Epoetin beta is shown to be safe and effective for the treatment of anemia in many patients with HRPC . It is found to improve QoL and physical functioning , and relieve fatigue symptoms , in many of these critically ill patients Abstract The aim of this study was to observe the symptom improvement and clinical benefit in elderly patients with advanced non-small cell lung cancer ( NSCLC ) stratified on the basis of CGA findings after treatment with a combination of traditional Chinese medicine and Western medicine .  Twenty-four elderly advanced NSCLC patients with a mean age of 73.0 ± 5.3 ( 65–83 ) years were categorized into three stratifications according to CGA results , namely function independent , mildly function impaired , and function dependent . They received st and ardized therapy , individualized therapy , and best supportive care , respectively . The patients receiving st and ardized therapy and individualized therapy were r and omized into two groups , with or without traditional Chinese medicine for symptom control , while for all the patients receiving best supportive care , traditional Chinese medicine was administered . Nine non-elderly NSCLC patients ( < 65 years old ) were enrolled as control and treated in accordance with NCCN NSCLC treatment guidelines . EORTC QLQ-C30 core scale , LC13 scale , and MDASI – TCM scale were used to assess relevant symptoms before and after treatment . After treatment for 3 weeks , it was shown by QLQ-C30+LC13 scales , for function-dependent patients , that the physical and role performances and the global health status were improved and the symptoms of fatigue and cough were alleviated ; by MDASI – TCM scale , the symptoms of fatigue , cough , and expectoration were improved . In function-independent and mildly function-impaired elderly patients , there were no significant changes in functional status and symptoms . But in non-elderly patients , the physical and social performances were lowered , and the symptoms of fatigue , constipation , and poor appetite were aggravated . The elderly patients with advanced NSCLC were categorized on the basis of CGA findings , and traditional Chinese medicine may be beneficial to symptom control of function-dependent patients The optimal hemoglobin concentration at which to initiate erythropoietic therapy for chemotherapy-induced anemia ( CIA ) is not well defined . This r and omized , open-label , multicenter study evaluated the ability of darbepoetin alfa ( 300 microg every 3 weeks ) to maintain hemoglobin levels > or = 10 g/dl in patients with CIA ( hemoglobin > or = 10.5 g/dl and < or = 12.0 g/dl ) r and omized 1:1 to an immediate-intervention group ( received darbepoetin alfa immediately ) or observation group ( received darbepoetin alfa if hemoglobin fell to < 10 g/dl ) . In 201 evaluable patients , there was a significant difference between the two groups in the Kaplan-Meier proportion of patients with a hemoglobin decrease to < 10 g/dl during weeks 1 - 13 ( test period ) ( primary endpoint ) : 29 % for immediate-intervention patients versus 65 % for observation patients . Sixty-four patients in the observation group received darbepoetin alfa ( delayed-intervention subgroup ) . The Kaplan-Meier proportion of patients who received transfusions was lower in the immediate-intervention group than in the delayed-intervention subgroup ( 14 % versus 31 % for the test period ; 17 % versus 36 % over the whole study ) . The target hemoglobin level ( > or = 11 g/dl ) was achieved by a higher percentage of patients ( crude percentage ) in less time in the immediate-intervention group ( 94 % in 2 weeks ) than in the delayed-intervention subgroup ( 73 % in 6 weeks ) ; hemoglobin endpoints for the delayed-intervention subgroup were calculated from recalibrated study week 1 ( the date patients first received darbepoetin alfa ) . For both groups , a higher mean change in hemoglobin from baseline led to a greater improvement in Functional Assessment of Cancer Therapy-Fatigue scores . In conclusion , immediate intervention result ed in a significantly lower proportion of patients who experienced a decline in hemoglobin , lower requirement for transfusions , and greater proportion of patients achieving and maintaining the target hemoglobin level PURPOSE The quality of life ( QOL ) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy ( RT ) . We assessed the effect of prophylactic d-threo-methylpheni date HCl ( d-MPH ) , a central nervous system ( CNS ) stimulant on QOL and cognitive function in patients undergoing RT . METHODS AND MATERIAL S Sixty-eight patients with primary or metastatic brain tumors were r and omly assigned to receive d-MPH or placebo . The starting dose of d-MPH was 5 mg twice daily ( b.i.d . ) and was escalated by 5 mg b.i.d . to a maximum of 15 mg b.i.d . The placebo was administered as one pill b.i.d . escalating three pills b.i.d . The primary outcome was fatigue . Patients were assessed at baseline , the end of radiation therapy , and 4 , 8 , and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue ( FACIT-F ) subscales , as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam . RESULTS The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm ( p = 0.61 ) . At 8 weeks after the completion of brain RT , there was no difference in fatigue between patient groups . The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm ( p = 0.64 ) . Secondary outcomes were not different between the two treatment arms . CONCLUSIONS Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL 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 PURPOSE A phase III , r and omized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass ( LBM ) , resting energy expenditure ( REE ) , and fatigue- and relevant secondary endpoints : appetite , quality of life , grip strength , Glasgow Prognostic Score ( GPS ) and proinflammatory cytokines . PATIENTS AND METHODS Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were r and omly assigned to one of five treatment arms : arm 1 , medroxyprogesterone ( 500 mg/day ) or megestrol acetate ( 320 mg/day ) ; arm 2 , oral supplementation with eicosapentaenoic acid ; arm 3 , L-carnitine ( 4 g/day ) ; arm 4 , thalidomide ( 200 mg/day ) ; and arm 5 , a combination of the above . Treatment duration was 4 months . RESULTS Analysis of variance showed a significant difference between treatment arms . A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints . An analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) significantly increased in arm 5 . REE decreased significantly and fatigue improved significantly in arm 5 . Appetite increased significantly in arm 5 ; interleukin (IL)-6 decreased significantly in arm 5 and arm 4 ; GPS and Eastern Cooperative Oncology Group performance status ( ECOG PS ) score decreased significantly in arm 5 , arm 4 , and arm 3 . Toxicity was quite negligible , and was comparable between arms . CONCLUSION The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite , IL-6 , GPS , and ECOG PS score was the combination regimen that included all selected agents Depression , anxiety and sleep disturbances are known problems in patients with breast cancer . The effect of melatonin as an antidepressant in humans with cancer has not been investigated . We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters : anxiety , sleep , general well-being , fatigue , pain and sleepiness . R and omized , double-blind , placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen , Denmark . Women , 30–75 years , undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory ( MDI ) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months . The primary outcome was the incidence of depressive symptoms measured by MDI . The secondary outcomes were area under the curve ( AUC ) for the subjective parameters . 54 patients were r and omized to melatonin ( n = 28 ) or placebo ( n = 26 ) and 11 withdrew from the study ( 10 placebo group and 1 melatonin group , P = 0.002 ) . The risk of developing depressive symptoms was significantly lower with melatonin than with placebo ( 3 [ 11 % ] of 27 vs. 9 [ 45 % ] of 20 ; relative risk 0.25 [ 95 % CI 0.077–0.80 ] ) , giving a NNT of 3.0 [ 95 % CI 1.7–11.0 ] . No significant differences were found between AUC for the subjective parameters . No differences in side effects were found ( P = 0.78 ) . Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery 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 Chemotherapy-induced peripheral neuropathy ( CIPN ) is common and leads to suboptimal treatment . Acetyl-L-carnitine ( ALC ) is a natural compound involved in neuronal protection . Studies have suggested ALC may be effective for the prevention and treatment of CIPN . PATIENTS AND METHODS A 24-week r and omized double-blind trial comparing ALC ( 3,000 mg per day ) with placebo in women undergoing adjuvant taxane-based chemotherapy  was conducted . The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity ( NTX ) component of the Functional Assessment of Cancer Therapy ( FACT ) -Taxane scale at 12 weeks . Secondary objectives included changes in 24-week end points , functional status ( FACT-Trial Outcome Index [ TOI ] ) , fatigue ( Functional Assessment of Chronic Illness Therapy [ FACIT ] -Fatigue ) , and NTX grade . RESULTS A total of 409 patients were evaluable ( 208 received ALC ; 201 , placebo ) . In a multivariate linear regression , week-12 scores were 0.9 points lower ( more CIPN ) with ALC than placebo ( 95 % CI , -2.2 to 0.4 ; P = .17 ) , whereas week-24 scores were 1.8 points lower with ALC ( 95 % CI , -3.2 to -0.4 ; P = .01 ) . Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores ( 38 % v 28 % ; P = .05 ) , and FACT-TOI scores were 3.5 points lower with ALC ( P = .03 ) . Grade 3 to 4 neurotoxicity was more frequent in the ALC arm ( eight v one ) . No differences between arms were observed for FACIT-Fatigue or other toxicities . Serum carnitine level increased with ALC but remained stable with placebo . CONCLUSION There was no evidence that ALC affected CIPN at 12 weeks ; however , ALC significantly increased CIPN by 24 weeks . This is the first study to our knowledge showing that a nutritional supplement increased CIPN . Patients should be discouraged from using supplements without proven efficacy BACKGROUND Probiotics may help resolve bowel symptoms and improve quality of life . We investigated the effects of 12 weeks of probiotics administration in colorectal cancer patients . METHODS We conducted a double-blind , r and omized , placebo-controlled trial . The participants took probiotics ( Lacidofil ) or placebo twice a day for 12 weeks . The cancer-related quality of life ( FACT ) , patient 's health-9 ( PHQ-9 ) , and bowel symptom question naires were completed by each participant . RESULTS We obtained data for 32 participants in the placebo group and 28 participants in the probiotics group . The mean ages of total participants were 56.18 ± .86 years and 58.3 % were male . Administration of probiotics significantly decreased the proportion of patients suffering from irritable bowel symptoms ( 0 week vs. 12 week ; 67.9 % vs. 45.7 % , p=0.03 ) , improved colorectal cancer-related FACT ( baseline vs. 12 weeks : 19.79 ± 4.66 vs. 21.18 ± 3.67 , p=0.04 ) and fatigue-related FACT ( baseline vs. 12 weeks : 43.00 ( 36.50 - 45.50 ) vs. 44.50 ( 38.50 - 49.00 ) , p=0.02 ) and PHQ-9 scores ( 0 weeks vs. 12 weeks ; 3.00 ( 0 - 8.00 ) vs. 1.00 ( 0 - 3.00 ) , p=0.01 ) . We found significant differences in changes of the proportion of patients with bowel symptoms ( p<0.05 ) , functional well-being scores ( p=0.04 ) and cancer-related FACT scores ( p=0.04 ) between the two groups . CONCLUSION Probiotics  improved bowel symptoms and quality of life in colorectal cancer survivors Abstract Under the common denomination of Systemic Immune-Metabolic Syndrome ( SIMS ) , we grouped many symptoms that share a similar pathophysiologic background . SIMS is the result of the dysfunctional interaction of tumor cells , stroma cells , and the immune system , leading to the release of cytokines and other systemic mediators such as eicosanoids . SIMS includes systemic syndromes such as paraneoplastic hemopathies , hypercalcemia , coagulopathies , fatigue , weakness , cachexia , chronic nausea , anorexia , and early satiety among others . Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states , but treatment 's compliance is generally poor . Preferentially , Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids , although their role in SIMS is unknown . The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach , some of the symptoms of the SIMS could be controlled . We exclusively evaluated 12 patients for compliance . Patients were assigned 1 of the 4 treatment groups ( 15- , 12- , 9- , or 6-g dose , fractionated every 8 h ) . For patients assigned to 15 and 12 doses , the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose . The maximum tolerable dose was calculated to be around 2 capsules tid ( 6 g of fish oil per day ) . A second cohort of 22 patients with advanced lung cancer and SIMS were r and omly assigned to receive either fish oil , 2 g tid , plus placebo capsules bid ( n = 12 ) or fish oil , 2 g tid , plus celecoxib 200 mg bid ( n = 10 ) . All patients in both groups received oral food supplementation . After 6 wk of treatment , patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite , less fatigue , and lower C-reactive protein ( C-RP ) values than their respective baselines values ( P < 0.02 for all the comparisons ) . Additionally , patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values ( P < 0.02 for all the comparisons ) . Comparing both groups , patients receiving fish oil + celecoxib showed significantly lower C-RP levels ( P = 0.005 , t-test ) , higher muscle strength ( P = 0.002 , t-test ) and body weight ( P = 0.05 , t-test ) than patients receiving fish oil + placebo . The addition of celecoxib improved the control of the acute phase protein response , total body weight , and muscle strength . Additionally , the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and /or celecoxib . This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor , some of the signs and symptoms associated with a SIMS could be ameliorated Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin ( FOLFOX ) or irinotecan plus 5-fluorouracil/leucovorin ( FOLFIRI ) has become a st and ard regimen for advanced or recurrent colorectal cancer . Numerous studies have reported that long-term use of FOLFOX or FOLFIRI leads to better survival for these patients . Thus , control of the toxicity of these drugs may be crucial to prolonging survival . Fucoidan is one of the major sulfated polysaccharides of brown seaweeds and exhibits a wide range of biological activities . In the present study , we analyzed the effect of fucoidan on suppressing the toxicity of anti-cancer drugs . A total of 20 patients with unresectable advanced or recurrent colorectal cancer scheduled to undergo treatment with FOLFOX or FOLFIRI  were r and omly allocated into a fucoidan treatment group ( n=10 ) and a control group without fucoidan treatment ( n=10 ) . Results showed that fucoidan regulated the occurrence of fatigue during chemotherapy . Chemotherapy with fucoidan was continued for a longer period than chemotherapy without fucoidan . Additionally , the survival of patients with fucoidan treatment was longer than that of patients without fucoidan , although the difference was not significant . Thus , fucoidan may enable the continuous administration of chemotherapeutic drugs for patients with unresectable advanced or recurrent colorectal cancer , and as a result , the prognosis of such patients is prolonged The purpose of this study was to assess whether the administration of recombinant human erythropoietin ( rHuEPO ) would correct anemia and improve the quality of life ( QOL ) in cancer patients receiving chemotherapy . One hundred twenty-two patients with hemoglobin < /=11.0 g/dl were r and omized to receive rHuEPO 10,000 U three times weekly ( n = 61 ) or no additional treatment ( n = 61 ) . Response was assessed by measuring changes in hemoglobin level and QOL . QOL was evaluated before each cycle of chemotherapy at baseline , Week 4 , and Week 12 using two separate self-report question naires . The analyses indicated that the rHuEPO-treated patients experienced significantly less fatigue ( P < 0.05 ) than their control group counterparts , and reported significantly higher scores on energy level ( P < 0.05 ) , ability to perform daily activities ( P < 0.01 ) , and overall QOL ( P < 0.05 ) . The overall change in hemoglobin level was significantly greater in the rHuEPO group than in the control group ( 1.7 g/dl versus 0.3 g/dl , P < 0.001 ) . rHuEPO effectively corrects anemia and significantly improves QOL in patients with solid tumors receiving chemotherapy Cancer‐related fatigue is a debilitating symptom affecting psychosocial functioning and quality of life in 70 % to 100 % of cancer patients during and after treatment . The authors examined the effect of 200 mg of modafinil daily on the severity of  cancer‐related fatigue Chemotherapy‐related anemia is prevalent among patients with hematologic malignancies . A r and omized , open‐label , multicenter trial of early versus late epoetin alfa in this population was conducted , focusing on quality of life ( QOL ) PURPOSE Fatigue is one of the most common symptoms experienced by patients with cancer . This trial was developed to evaluate the efficacy of long-acting methylpheni date for improving cancer-related fatigue and to assess its toxicities . PATIENTS AND METHODS Adults with cancer were r and omly assigned in a double-blinded manner to receive methylpheni date ( target dose , 54 mg/d ) or placebo for 4 weeks . The Brief Fatigue Inventory was the primary outcome measure , while secondary outcome measures included a Symptom Experience Diary ( SED ) , the Short Form-36 ( SF-36 ) Vitality Subscale , a linear analog self- assessment , the Pittsburgh Sleep Quality Index , and the Subject Global Impression of Change . RESULTS In total , 148 patients were enrolled . Using an area under the serum concentration-time curve analysis , there was no evidence that methylpheni date , as compared with placebo , improved the primary end point of cancer-related fatigue in this patient population ( P = .35 ) . Comparisons of secondary end points , including clinical ly significant changes in quality -of-life variables and cancer-related fatigue change from baseline , were similarly negative . However , a subset analysis suggested that patients with more severe fatigue and /or with more advanced disease did have some fatigue improvement with methylpheni date ( eg , in patients with stage III or IV disease , the mean improvement in usual fatigue was 19.7 with methylpheni date v 2.1 with placebo ; P = .02 ) . There was a significant difference in self-reported toxicities ( SED ) , with increased levels of nervousness and appetite loss in the methylpheni date arm . CONCLUSION This clinical trial was unable to support the primary pre study hypothesis that the chosen long-acting methylpheni date product would decrease cancer-related fatigue 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 This dose-finding , placebo-controlled study evaluated the safety and efficacy of darbepoetin alfa administered every 3 weeks ( Q3W ) to anaemic patients receiving chemotherapy . In part A , patients ( haemoglobin < /=110 g/l ) were r and omised in a 1:4 ratio to receive 1 of 6 doses of darbepoetin alfa ( 4.5 , 6.75 , 9.0 , 12.0 , 13.5 and 15.0 microg/kg ) or placebo Q3W for 12 weeks . In part B , patients received open-label darbepoetin alfa .  Patients ( n=249 ) were evaluated for safety , haemoglobin endpoints and red blood cell ( RBC ) transfusions .  Darbepoetin alfa given at doses ranging from 4.5 to 15.0 microg/kg Q3W was well tolerated and comparable to placebo in terms of safety . No neutralising antibodies were detected . All doses ( from 4.5 to 15 microg/kg ) reduced transfusions compared with placebo , and result ed in > 50 % of patients achieving a haematopoietic response . Administration of darbepoetin alfa Q3W has a tolerable safety profile and effectively ameliorates anaemia due to chemotherapy ABSTRACT Fatigue is a common symptom in patients with head and neck carcinoma who undergo chemoradiotherapy . Guarana ( Paullinia cupana ) is a plant that grows in the Brazilian Amazon region that was used previously to treat fatigue induced by chemotherapy . Methods : In this phase II prospect i ve study , we evaluated 60 patients with stage I – IV head and neck squamous cell carcinoma before , during , and after chemoradiotherapy .  The patients were r and omized into two arms : placebo versus guarana at a dose of 50 mg twice a day during the chemoradiotherapy treatment . We used the FACT-HN , EORTC-HN35 , and EORTC-Q30 question naires to assess fatigue and quality of life ( QOL ) . Results : A significant worsening of QOL in the overall ( p = 0.0054 ) , functional ( p = 0.018 ) , and symptom ( p = 0.0042 ) domains after the second cycle of chemotherapy was observed in patients using guarana compared to the placebo group . No significant differences in any QOL domain for either the guarana or placebo group were observed when the first and the fourth evaluations of each domain in each group were compared . Regarding the FACT-HN35 question naire , the guarana group showed improvement after the first cycle of chemoradiotherapy with respect to pain ( p = 0.0133 ) , social eating ( p = 0.0227 ) , swallowing ( p = 0.0254 ) , coughing ( p = 0.0107 ) , and weight loss ( p = 0.012 ) ; however , after treatment completion ( after the third cycle ) weight loss worsened ( p = 0.0074 ) and greater use of a nasogastric tube ( p = 0.051 ) , in addition to increased use of analgesics ( p = 0.0253 ) , was observed in the guarana group . Regarding the EORTC-QOL C30 question naire , improvement of symptoms in the three domains ( functional , overall , and symptoms ) was observed in patients using guarana . No significant difference was observed between the groups regarding toxicity as grade d by the Common Terminology Criteria for Adverse Events ( CTCAE ) scale . Conclusion : We propose that guarana is not beneficial for this patient population Purpose Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy .  Acetylcholinesterase inhibitors ( AChEI ) may improve cognitive impairment . We conducted a r and omized , placebo-controlled , pilot study to assess the feasibility of using the AChEI , donepezil , to improve subjective and objective measures of cognitive function in breast cancer survivors . Methods Women who received adjuvant chemotherapy 1–5 years prior with current cognitive dysfunction symptoms were r and omized to  5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks . A battery of vali date d measures of attention , memory , language , visuomotor skills , processing speed , executive function , and motor dexterity and speed was administered at baseline and at 24 and 36 weeks . Subjective cognitive function , fatigue , sleep , mood , and health-related quality of life were evaluated at baseline and at 12 , 24 , and 36 weeks . Results Sixty-two patients were enrolled , 76 % completed the study , self-reported compliance was 98 % , and toxicities were minimal . At the end of treatment , the donepezil group performed significantly better than the control group on two parameters of memory — the Hopkins Verbal Learning Test -Revised ( HVLT-R ) Total Recall ( p = 0.033 ) and HVLT-R Discrimination ( p = 0.036 ) . There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life . Conclusion Accrual to this feasibility trial was robust , retention was good , compliance was excellent , and toxicities were minimal . Implication s for Cancer SurvivorsR and omized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible . A phase III trial testing the efficacy of donepezil is warranted given these pilot results 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 Anemia in patients receiving chemotherapy can be ameliorated with recombinant human erythropoietin ( rHuEPO ) , which is administered one to three times per week . Darbepoetin α , a new erythropoietic agent , has longer serum residence time , allowing it to be administered less frequently Purpose Modafinil has been reported to benefit a subgroup of patients suffering severe fatigue while undergoing chemotherapy . Docetaxel is associated with fatigue that may lead to premature therapy withdrawal . We investigated whether modafinil could reduce fatigue during docetaxel chemotherapy . Methods This multicenter , r and omized , double-blind , placebo-controlled study evaluated the efficacy of modafinil in patients with metastatic prostate or breast cancer undergoing docetaxel chemotherapy ( every 21 days ; minimum dose 50 mg/m2 ) . At the start of their third or subsequent chemotherapy cycle , patients with significant docetaxel-associated fatigue were r and omized to receive concurrent modafinil 200 mg/day or placebo for 15 days ( “ treatment periods ” ( TP ) ) . Docetaxel was continued for up to four further cycles . Fatigue was evaluated with the fatigue component of the MD And erson Symptom Inventory ( MDASI ) . The primary endpoint was cumulative MDASI area under the curve ( AUC ) during the first 7 days of study medication during TP1 and TP2 . Results Evaluable data were available from 83 patients ( 65 with prostate cancer ) . There was no statistically significant difference between the two treatment arms for the primary endpoint ( MSADI AUC3–10 35.9 vs 39.6 ; 95 % confidence interval −8.9 , 1.4 ; P = 0.15 ) . Overall toxicity was comparable between treatment groups ; however , the incidence of grade ≤2 nausea and vomiting was higher in the modafinil arm ( 45.4 vs 25 % ) . Conclusions Assessing and managing chemotherapy-related fatigue remains a major challenge . There was a lack of difference between the two arms in the planned primary endpoint . However , there was a modest but consistent trend towards improvement of docetaxel-related fatigue in those treated with modafinil . Based on the study findings , modafinil for the treatment of fatigue associated with docetaxel chemotherapy elicits modest improvements . Larger , longer term , r and omized , controlled studies are required to clarify the exact role of modafinil in the treatment of docetaxel-related fatigue 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 A r and omised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate ( MA ) on the quality of life ( QoL ) , appetite , weight and survival of patients with advanced , incurable , hormone-insensitive cancer .  QoL was assessed at the start of treatment and at 4 , 8 and 12 weeks , using the EORTC-QLQ-C30 instrument . 255 patients were r and omised to 320 mg of MA daily or placebo  for 12 weeks . 244 patients were assessable at baseline , 190 at 4 weeks ( placebo 94 ; MA 96 ) , 150 at 8 weeks ( placebo 69 ; MA 81 ) and 112 at 12 weeks ( placebo 55 ; MA 57 ) . A beneficial effect of MA on appetite loss was observed at week 4 ( P < 0.0001 ) and possibly at week 8 ( P = 0.058 ) . Further weight loss during treatment was significant only in the placebo group . In the first 8 weeks , changes in mean global QoL were small and similar in both groups . By 12 weeks the decrease in mean global QoL was more pronounced in the MA group ( P = 0.028 ) , which was related to a deterioration in physical function , while psychosocial function was not affected . Survival was not affected by MA , and side-effects were mild . The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity . However , MA does not appear to improve global QoL as measured by the EORTC QLQ-C30 PURPOSE To evaluate the effect of epoetin alfa on local disease-free survival ( DFS ) , overall survival ( OS ) , and cancer treatment-related anemia and fatigue in patients with head and neck cancer receiving radical radiotherapy with curative intent . PATIENTS AND METHODS Patients ( N = 301 ) with hemoglobin ( Hb ) less than 15 g/dL were r and omly assigned in a ratio of 1:1 to receive radiotherapy plus epoetin alfa ( 10,000 U subcutaneously [ SC ] three times weekly if baseline Hb was < 12.5 g/dL ; 4,000 U SC three times weekly if baseline Hb > or = 12.5 g/dL ) or radiotherapy alone .  Hb levels were monitored weekly . The primary end point was local DFS , defined as the time from r and om assignment to local disease recurrence or death . Secondary efficacy end points included OS , local tumor response , and local tumor control . Patients were followed at 1 , 4 , 8 , and 12 weeks postradiotherapy and annually for 5 years . Cancer treatment-related anemia and fatigue were evaluated with the Functional Assessment of Cancer Therapy-Anemia and Functional Assessment of Cancer Therapy-Head and Neck . Adverse events were recorded up to 12 weeks postradiotherapy . RESULTS Hb levels increased from baseline with epoetin alfa . The median duration of local DFS was not statistically different between groups ( observation , 35.42 months ; epoetin alfa , 31.47 months ; hazard ratio , 1.04 ; 95 % CI , 0.77 to 1.41 ) . Groups did not significantly differ in DFS , OS , tumor outcomes , or cancer treatment-related anemia or fatigue . No new or unexpected adverse events were observed . CONCLUSION Addition of epoetin alfa to radical radiotherapy did not affect survival , tumor outcomes , anemia , or fatigue positively or negatively in patients with head and neck cancer In order to pilot a study observing the feasibility of applying the Core Quality of Life Question naire ( QLQ-C30 ) version 2.0 to assess the quality of life ( QOL ) of patients with NSCLC treated with Feiji Recipe , a r and omized , parallel controlled clinical trial was conducted in the university-affiliated hospital . Seventy in patients who met the inclusion criteria were r and omized into the study , and 60 cases were available as subjects for QOL data analysis . The subjects were r and omly assigned to one of three groups : the Feiji Recipe group ( A ) ; the Feiji Recipe combined with chemotherapy group ( B ) ; and the chemotherapy group ( C ) in which the patients were treated with vinorelbine plus cisplatin ( NP ) or gemcitabine plus cisplatin ( GP ) .  QOL was assessed with the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 . Sixty cases that finished the question naires were analyzed , and we found that patients who received chemotherapy had low QOL , in terms of their global health , role , emotional , social , economic status and symptom burden including fatigue , nausea and vomiting , dyspnea , loss of appetite and abnormal bowel movements . Simultaneous treatment with Feiji Recipe and chemotherapy was able to prevent the worsening of function in terms of role , social , fatigue and global health . The Core Quality of Life Question naire ( QLQ-C30 ) version 2.0 can be used to evaluate the QOL of patients with NSCLC treated by Chinese herbal medicine .  Feiji Recipe might partially improve the QOL of NSCLC patients when administered alone or in combination with chemotherapy . No unexpected side effects were observed . However , further double-blinded placebo controlled studies are strongly recommended OBJECTIVE This analysis of the results of a r and omized , controlled trial evaluating the effects of epoetin alfa ( EPO ) therapy on transfusion requirements , hemoglobin ( Hb ) , and quality of life ( QOL ) in patients with cancer receiving platinum-based chemotherapy was conducted to evaluate the effect of initial Hb level on study outcomes . METHODS Patients with Hb levels < or = 12.1 g/dl were r and omized 2:1 to receive EPO , 10,000 U three times weekly s.c . or best supportive care ( BSC ) until 4 weeks after their last chemotherapy cycle . For this analysis , patients were stratified by baseline Hb level ( < or = 9.7 g/dl , > 9.7 g/dl to < or = 10.5 g/dl , > 10.5 g/dl to < or = 11.3 g/dl , and > 11.3 g/dl to < or = 12.1 g/dl ) , and study results were reanalyzed . RESULTS Significantly fewer EPO patients than BSC patients with initial Hb levels > 9.7 g/dl to < or = 12.1 g/dl required transfusions . EPO  maintained Hb levels throughout the study for patients with Hb levels > 11.3 g/dl to < or = 12.1 g/dl , compared with a decrease with BSC . For patients with baseline Hb levels > 10.5 g/dl , for whom the mean changes from baseline to last assessment were measured by the Cancer Linear Analogue Scale assessment s of energy and overall QOL as well as by the Functional Assessment of Cancer Therapy (FACT)-Fatigue and FACT-An Anemia subscale , QOL scores were significantly greater with EPO than with BSC .  QOL declined in patients receiving BSC , and the mean decreases in QOL scores were greater for BSC patients with baseline Hb levels > 10.5 g/dl , compared with the overall BSC group . CONCLUSION In patients with cancer receiving platinum-based chemotherapy and with baseline Hb levels > 10.5 g/dl , early intervention with EPO reduces transfusions , maintains Hb level , and maintains or improves QOL . This study supports the positive effects of early intervention when analyzed according to initial Hb value 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 BACKGROUND Nutritional interventions have shown increased energy intake but not improvement in health-related quality of life ( HRQL ) or prognosis in non small cell lung cancer ( NSCLC ) patients . Eicosapentaenoic acid has been proposed to have anti-inflammatory , anticachectic and antitumoural effects . OBJECTIVE To compare the effect of an oral EPA enriched supplement with an isocaloric diet on nutritional , clinical and inflammatory parameters and HRQL in advanced NSCLC patients . DESIGN Patients with advanced NSCLC were r and omized to receive diet plus oral nutritional supplement containing EPA ( ONS-EPA ) or only isocaloric diet ( C ) . All patients received paclitaxel and cisplatin/carboplatin treatment . Weight , body composition , dietary intake , inflammatory parameters and HRQL were assessed at baseline and after the first and second cycles of chemotherapy . Response to chemotherapy and survival were evaluated . RESULTS Ninety two patients were analysed ( 46 ONS-EPA,46 C ) . ONS-EPA group had significantly greater energy ( p < 0.001 ) and protein ( p < 0.001 ) intake compared with control . Compared with baseline , patients receiving the ONS-EPA gained 1.6 ± 5 kg of lean body mass ( LBM ) compared with a loss of -2.0 ± 6 kg in the control ( p = 0.01 ) . Fatigue , loss of appetite and neuropathy decreased in the ONS-EPA group ( p ≤ 0.05 ) . There was no difference in response rate or overall survival between groups . CONCLUSION Patients with NSCLC receiving ONS-EPA  significantly improves energy and protein intake , body composition . and decreased fatigue , loss of appetite and neuropathy . Registered with Clinical Trials.gov ( NCT01048970 ) PURPOSE Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic radiotherapy ? MATERIAL AND METHODS Fifty-six patients with an indication for adjuvant pelvic irradiation after curative surgery were double-blind r and omized . All patients took 3 x 4 capsules study medication daily during radiotherapy . Twenty-eight patients in the enzyme group ( EG ) received capsules containing papain , trypsin and chymotrypsin , 28 in the placebo group ( PG ) received placebo capsules . All patients were irradiated with 5 x 1.8 Gy weekly to 50.4 Gy using four-field-box technique after CT-based planning . Primary objective was the grade of diarrhea , nausea , vomiting , fatigue and epitheliolysis during radiotherapy . Secondary objectives were the number of supportive medications and treatment interruptions due to acute toxicity . RESULTS None/mild diarrhea : 43 % EG , 64 % PG . Moderate/severe diarrhea : 57 % EG , 36 % PG ( P = 0.11 ) . Mean duration : 11 days in EG , 10 days in PG . None/mild nausea : 93 % EG , 93 % PG . Moderate/severe nausea : 7 % EG , 7 % PG . None/mild vomiting : 100 % EG , 97 % PG . None/mild fatigue : 82 % EG , 93 % PG . Moderate/severe fatigue : 18 % EG , 7 % PG ( P = 0.23 ) . None/mild epitheliolysis : 75 % EG , 93 % PG . Moderate/severe epitheliolysis : 25 % EG , 7 % PG ( P = 0.16 ) . Treatment interruption ( mean days ) : 2.44 in EG , 1.46 in PG . Number of supportive medication : 29 in EG , 19 in PG . CONCLUSIONS The prophylactic use of proteolytic enzymes does not reduce acute toxicities , treatment interruptions and number of supportive medication and therefore does not improve tolerance of adjuvant pelvic radiotherapy PURPOSE Corticosteroids are frequently used in cancer pain management despite limited evidence . This study compares the analgesic efficacy of corticosteroid therapy with placebo . PATIENTS AND METHODS Adult patients with cancer receiving opioids with average pain intensity ≥ 4 ( numeric rating scale [ NRS ] , 0 to 10 ) in the last 24 hours were eligible . Patients were r and omly assigned to methylprednisolone ( MP ) 16 mg twice daily or placebo ( PL ) for 7 days . Primary outcome was average pain intensity measured at day 7 ( NRS , 0 to 10 ) ; secondary outcomes were analgesic consumption ( oral morphine equivalents ) , fatigue and appetite loss ( European Organisation for Research and Treatment of Cancer- Quality of Life Question naire C30 , 0 to 100 ) , and patient satisfaction ( NRS , 0 to 10 ) . RESULTS A total of 592 patients were screened ; 50 were r and omly assigned , and 47 were analyzed . Baseline opioid level was 269.9 mg in the MP arm and 160.4 mg in the PL arm . At day-7 evaluation , there was no difference between the groups in pain intensity ( MP , 3.60 v PL , 3.68 ; P = .88 ) or relative analgesic consumption ( MP , 1.19 v PL , 1.20 ; P = .95 ) . Clinical ly and statistically significant improvements were found in fatigue ( -17 v 3 points ; P .003 ) , appetite loss ( -24 v 2 points ; P = .003 ) , and patient satisfaction ( 5.4 v 2.0 points ; P = .001 ) in favor of the MP compared with the PL group , respectively . There were no differences in adverse effects between the groups . CONCLUSION MP 32 mg daily did not provide additional analgesia in patients with cancer receiving opioids , but it improved fatigue , appetite loss , and patient satisfaction . Clinical benefit beyond a short-term effect must be examined in a future study Carnitine deficiency is prevalent in population s with chronic illness , including cancer . In a recent open-label study , L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients . To further evaluate this finding , adult patients with advanced cancer , carnitine deficiency ( free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females , or acyl/free carnitine ratio of more than 0.4 ) , moderate to severe fatigue , and a Karnofsky Performance Status ( KPS ) score of 50 or more , were r and omly assigned to receive either L-carnitine ( 0.5 g/day for two days , followed by 1g/day for two days , and then 2g/day for 10 days ) or placebo . This double-blind phase was followed by an open-label phase , during which all patients received L-carnitine supplementation for two weeks . Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) , the Linear Analog Scale Assessment s ( LASA ) , the Mini-Mental State Exam ( MMSE ) , and the KPS .  Twenty-nine patients ( 12 placebo , 17 L-carnitine )  were included in the intent-to-treat ( ITT ) analysis . From baseline to the end of the double-blind phase , serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 ( P=0.004 ) , and from 22.9+/-19.4 to 45.3+/-17.2 ( P=0.004 ) , respectively , in the L-carnitine-treated group , and from 28.2+/-10.2 to 36.2+/-8.7 ( P = ns ) , and from 22.6+/-7.9 to 28.7+/-8.6 ( P = ns ) in the placebo group , respectively . The planned ITT analysis revealed no significant improvement in any of the study 's endpoints , and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated . However , an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale ( P<0.03 ) , and significantly improved FACT-An functional well-being subscale ( P<0.03 ) , and KPS ( P<0.003 ) , in the group that started with L-carnitine during the double-blind phase . These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients . However , L-carnitine supplementation does increase L-carnitine serum levels , and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a sub population of cancer patients BACKGROUND Common acute-term side effects of brain radiotherapy ( RT ) include fatigue , drowsiness , decreased physical functioning , and decreased quality of life ( QOL ) . We hypothesized that armodafinil ( a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy ) would result in reduced fatigue and sleepiness for patients receiving brain RT . METHODS A phase II , multi-institutional , placebo-controlled r and omized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT  , from whom we obtained estimates of variability for fatigue , sleepiness , QOL , cognitive function , and treatment effect . RESULTS From September 20 , 2010 , to October 20 , 2012 , 54 participants enrolled with 80 % retention and 94 % self-reported compliance . There were no grade 4 - 5 toxicities , and the incidence of grade 2 - 3 toxicities was similar between treatment arms , the most common of which were anxiety and nausea ( 15 % ) , headaches ( 19 % ) , and insomnia ( 20 % ) . There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes ( Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue , Brief Fatigue Inventory , Epworth Sleepiness Scale , FACT-Brain , and FACIT-cognitive function ) . However , in participants with more baseline fatigue , those treated with armodafinil did better than those who received the placebo on the end-RT assessment s for several outcomes . CONCLUSION Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance . While there was no overall significant effect on fatigue , those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil . These data suggest that a prospect i ve , phase III r and omized trial is warranted for patients with greater baseline fatigue BACKGROUND Fatigue is common among glioma patients undergoing radiotherapy ( RT ) and impacts quality of life ( QOL ) . We evaluated whether armodafinil , a wakefulness-promoting medication , improves fatigue in glioma patients undergoing RT . METHODS Eligibility criteria included age ≥18 years , Karnofsky performance status ≥60 , and grade 2 - 4 glioma undergoing RT to a total dose of 50 - 60 Gy . Patients were r and omized 1:1 to armodafinil or placebo for 8 weeks beginning within 10 days of starting RT . Fatigue and QOL were assessed at baseline , day 22 , day 43 , and day 56 with the Functional Assessment of Chronic Illness Therapy - Fatigue ( FACIT-F ) , the Functional Assessment of Cancer Therapy - General ( FACT-G ) , the Brief Fatigue Inventory ( BFI ) , and the Cancer Fatigue Scale ( CFS ) . The primary aim was to detect a difference in the 42-day change in FACIT-F fatigue subscale between the 2 groups using a 2- sample Wilcoxon statistic . RESULTS We enrolled 81 patients total ( 42 armodafinil and 39 placebo ) .  Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale , FACT-G , CFS , or BFI . Further analysis suggests no difference between the arms even after accounting for the potential bias of missing data . Treatment was well tolerated with few grade 3 or 4 toxicities . CONCLUSIONS While treatment was well-tolerated , an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study . Further studies are needed to determine whether pharmacologic treatment improves fatigue in glioma patients undergoing RT CONTEXT Dyspnea is one of the most distressing symptoms in patients with cancer , and often worsens with breakthrough episodes on exertion . We hypothesized that fentanyl given prophylactically may alleviate breakthrough dyspnea . OBJECTIVES To determine the feasibility of conducting a r and omized trial of subcutaneous fentanyl in patients with cancer , and examine the effects of fentanyl on dyspnea , walk distance , vital signs , and adverse events . METHODS In this double-blind , r and omized , controlled trial , we asked ambulatory patients with breakthrough dyspnea to perform a baseline six minute walk test ( 6MWT ) , and then assigned them to either subcutaneous fentanyl or placebo 15 minutes before a second 6MWT . We documented the change in dyspnea Numeric Rating Scale ( NRS ) score , walk distance , vital signs , and adverse events between the first and second 6MWT . RESULTS A total of 20 patients were enrolled ( 1:1 ratio ) without attrition . Comparison between baseline and second walk showed that fentanyl was associated with significant improvements in dyspnea NRS score at the end of the 6MWT ( mean [ 95 % CI ] -1.8 [ -3.2 , -0.4 ] ) , dyspnea NRS score at rest of 15 minutes after drug administration ( -0.9 [ -1.8 , -0.04 ] ) , Borg Scale fatigue score at the end of the 6MWT ( -1.3 [ -2.4 , -0.2 ] ) , 6MWT distance ( + 37.2 m [ 5.8 , 68.6 ] ) , and respiratory rate ( -2.4 [ -4.5 , -0.3 ] ) . Nonstatistically significant improvements also were observed in the placebo arm , with no difference between the two study arms . No significant adverse effects were observed . CONCLUSION Prophylactic fentanyl was safe and improved dyspnea , fatigue , walk distance , and respiratory rate . We also observed a large placebo effect . Our results justify larger r and omized controlled trials with higher fentanyl doses ( clinical trials.gov registration : NCT01515566 ) PURPOSE To investigate the effects of medroxyprogesterone acetate ( MPA ) on appetite , weight , and quality of life ( QL ) in patients with advanced-stage , incurable , non-hormone-sensitive cancer . PATIENTS AND METHODS Two hundred six eligible patients were r and omized between double-blind MPA 500 mg twice daily or placebo .  Appetite ( 0 to 10 numerical rating scale ) , weight , and QL ( European Organization for Research and Treatment of Cancer Quality of Life Question naire [ EORTC-QLQ-C30 ] ) were assessed before the start of treatment ( t = 0 ) , and 6 weeks ( t = 6 ) and 12 weeks ( t = 12 ) thereafter . RESULTS One hundred thirty-four patients ( 68 MPA and 66 placebo ) were assessable at t = 6 and 99 patients ( 53 MPA and 46 placebo ) at t = 12 . A beneficial effect of MPA on appetite was observed after both 6 weeks ( P = .008 ) and 12 weeks ( P = .01 ) of treatment . After 12 weeks , a mean weight gain of 0.6 + /- 4.4 kg was seen in the MPA , versus an ongoing mean weight loss of 1.4 + /- 4.6 kg in the placebo group . This difference of 2.0 kg was statistically significant ( P = .04 ) . During the study , several areas of QL deteriorated in the total group of patients . With the exception of an improvement in appetite and possible also a reduction in nausea and vomiting , no measurable beneficial effects of MPA on QL could be demonstrated . The side effects profile of MPA was favorable : only a trend toward an increase in ( usually mild ) peripheral edema was observed . CONCLUSION In weight-losing , advanced-stage non-hormone-sensitive cancer patients , MPA exhibits a mild side effects profile , has a beneficial effect on appetite , and may prevent further weight loss . However , general QL in the present study was not measurably influenced by MPA treatment The aim of the study was to investigate the effects of erythropoietin ( epoetin beta ) on red blood cell ( RBC ) transfusions , hemoglobin ( Hb ) levels , and quality of life ( QOL ) in patients with relapsed lymphoma treated with an aggressive sequential salvage chemotherapy ( SSCT ) regimen . Sixty patients with early or late relapsed Hodgkin 's disease ( n=39 ) or first relapse of aggressive non-Hodgkin 's lymphoma ( n=21 ) were r and omized to receive epoetin beta 10,000 IE subcutaneously three times a week or no epoetin during salvage chemotherapy . Patients in both study arms received two cycles of DHAP ( dexamethasone , high-dose cytarabine , cisplatin ) ; patients in partial remission ( PR ) or complete remission ( CR ) then received cyclophosphamide , followed by peripheral blood stem cell ( PBSC ) harvest , methotrexate plus vincristine , and etoposide . The final myeloablative course was BEAM ( carmustine , etoposide , cytarabine , and melphalan ) followed by autologous stem cell support . The primary endpoint of the study was the number of RBC units needed during SSCT . In addition , Hb levels and QOL were measured . The mean number of RBC units given in the epoetin beta arm was 4.5 compared to 8.3 in the control arm ( P=0.0134 ) . The mean Hb levels during therapy were 10.4 g/dl in the epoetin beta arm and 9.7 g/dl in the control ( P=0.018 ) . From baseline until BEAM therapy QOL ( EORTC QLQ C30 ) and fatigue ( MFI ) assessment showed little QOL worsening or stable levels in both arms with a steeper increase of fatigue levels in the control group . Patients with relapsed lymphoma undergoing aggressive chemotherapy and stem cell support benefited from epoetin beta therapy , with a decrease of RBC transfusion requirements and lower rise of fatigue levels This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks ( Q3W ) at fixed doses of 300 or 500 μg with or without intravenous ( IV ) iron in treating anemia in patients receiving multicycle chemotherapy . This Phase 2 , double‐blind , 2 × 2 factorial study r and omized patients to one of four treatment arms ; darbepoetin alfa 300 μg  ( n = 62 ) , darbepoetin alfa 300 μg plus IV iron ( n = 60 ) , darbepoetin alfa 500 μg ( n = 60 ) , or darbepoetin alfa 500 μg plus IV iron ( n = 60 ) . Patients had nonmyeloid malignancies , hemoglobin levels ≤10 g dL−1 , and no iron deficiency . Primary endpoint was achievement of target hemoglobin ( ≥11 g dL−1 ) . Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue ( FACT‐F ) score from baseline to end of study . Safety was evaluated by incidence of adverse events . No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed , therefore , results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups . Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin ( 75 and 78 % , respectively ) ; Kaplan – Meier median time to target hemoglobin was 10 and 8 weeks , respectively . More patients receiving IV iron ( 82 % ) than not receiving IV iron ( 72 % ) achieved hemoglobin target . Adverse events profiles were similar for darbepoetin alfa treatment groups . Transient anaphylactoid reactions were reported in two patients receiving IV iron . Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit , while added IV iron  improved treatment response in these patients . Am . J. Hematol . , 2010 . © 2010 Wiley‐Liss , PURPOSE To determine whether epoetin alfa reduces anemia-related fatigue , improves other aspects of health-related patient-recorded outcomes ( PROs ) , reduces the number of RBC transfusions , and has an impact on freedom from treatment failure ( FFTF ) and overall survival ( OS ) in patients with advanced-stage Hodgkin 's lymphoma ( HL ) . PATIENTS AND METHODS The prospect ively r and omized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy ( six to eight cycles of bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , and prednisone [ BEACOPP ] ) in a double-blind , placebo-controlled setting . The study accrued 1,379 patients , of whom 1,328 were assessable for safety , 1,303 were assessable for clinical outcome , and 930 were assessable for PROs . RESULTS PROs were not different in patients receiving placebo or epoetin alfa , both after the end of chemotherapy and 6 months thereafter . There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS . There were also no differences in the numbers of deaths , progressions , relapses , and thromboembolic events . The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group ( P < .001 ) , with 27.4 % of patients needing no RBC transfusion in the placebo group compared with 36.7 % of patients in the epoetin alfa group ( P < .001 ) . CONCLUSION Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains
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 ) .