Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial. Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease. Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin Beta, in hematologic malignancies. A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multicentre, randomised trial Effect of paroxetine hydrochloride (Paxil®) on fatigue and depression in breast cancer patients receiving chemotherapy Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. Course of fatigue in women receiving chemotherapy and/or radiotherapy for early stage breast cancer. Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. Supportive intervention for fatigue in patients undergoing chemotherapy: a randomized controlled trial. Fatigue, depression and quality of life in cancer patients: how are they related? Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Feasibility of quantifying the effects of epoetin alfa therapy on cognitive function in women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy. Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. Comparison between fatigue, sleep disturbance, and circadian rhythm in cancer inpatients and healthy volunteers: evaluation of diagnostic criteria for cancer-related fatigue. Use of a case definition approach to identify cancer-related fatigue in women undergoing adjuvant therapy for breast cancer. Effect of recombinant human erythropoietin on quality of life in cancer patients receiving chemotherapy: results of a randomized, controlled trial. Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia. Darbepoetin alfa administered every 3 weeks alleviates anaemia in patients with solid tumours receiving chemotherapy; results of a double-blind, placebo-controlled, randomised study. Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial. Prevention of Anemia in Patients with Solid Tumors Receiving Platinum-Based Chemotherapy by Recombinant Human Erythropoietin (rHuEpo): A Prospective, Open Label, Randomized Trial by the Hellenic Cooperative Oncology Group Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy. Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study. Recombinant human erythropoietin, epoetin beta, in patients with relapsed lymphoma treated with aggressive sequential salvage chemotherapy—results of a randomized trial
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 PURPOSE Cancer treatment-related fatigue is the most prevalent and distressing symptom of cancer therapy . Interventions to minimize fatigue are needed . The purpose of this study was to examine the relationship between exercise and fatigue over the first three cycles of chemotherapy in women receiving either cyclophosphamide , methotrexate , and fluorouracil ( CMF ) or doxorubicin and cyclophosphamide ( AC ) for breast cancer . METHODS Seventy-two newly diagnosed women with breast cancer were instructed in a home-based moderate-intensity exercise intervention . Measures of functional ability , energy expenditure , and fatigue were obtained at baseline and posttest . Subjects maintained daily records of four types of fatigue , and exercise duration , intensity , and type . RESULTS Exercise significantly reduced all four levels of fatigue ( P < 0.01 ) . As the duration of exercise increased , the intensity of fatigue declined ( P < 0.01 ) . There was a significant carry-over effect of exercise on fatigue , but the effect lasted only 1 d. The level of fatigue at study entry was not associated with number of days of exercise or amount of exercise a woman engaged in . CONCLUSIONS The impact of exercise on fatigue was significant and suggests the effectiveness of a low- to moderate-intensity regular exercise program in maintaining functional ability and reducing fatigue in women with breast cancer receiving chemotherapy BACKGROUND Fatigue is a commonly encountered symptom of human immunodeficiency virus ( HIV ) disease , associated with significant psychological and functional morbidity and poor quality of life . Preliminary studies on the treatment of fatigue from the cancer and multiple sclerosis literature suggest that psychostimulants may be effective in reducing fatigue . OBJECTIVE To compare the efficacy of 2 psychostimulant medications , methylpheni date hydrochloride ( Ritalin ) and pemoline ( Cylert ) , with a placebo intervention for the treatment of fatigue in patients with HIV disease . METHODS In this double-blind trial , 144 ambulatory patients with HIV disease and persistent and severe fatigue were r and omized to treatment with methylpheni date , pemoline , or placebo . Medications were titrated up to a maximum dose of 60 mg of methlypheni date hydrochloride , 150 mg of pemoline , or 8 capsules of placebo daily . Fatigue was measured using 2 self-reported rating scales , the Piper Fatigue Scale ( PFS ) and the Visual Analogue Scale for Fatigue ( VAS-F ) . We also used the timed isometric unilateral straight leg-raising task , a measure of muscular endurance . Quality -of-life and psychological well-being measures included the Beck Depression Inventory , the Brief Symptom Inventory , and the 36-Item Short-Form Medical Outcomes Study Health Status Survey . Side effects were monitored using the Systematic Assessment for Treatment Emergent Events and the Extra-pyramidal Symptom Rating Scale . All measures were rated weekly . RESULTS One hundred nine subjects completed the 6-week trial ; 15 patients ( 41 % ) receiving methylpheni date and 12 patients ( 36 % ) receiving pemoline demonstrated clinical ly significant improvement compared with 6 patients ( 15 % ) receiving placebo . Patients receiving methylpheni date or pemoline demonstrated significantly more improvement in fatigue on several self-reported rating scales ( PFS total score , P=.04 ; affective subscale , P=.008 ; sensory subscale , P=.04 ; and VAS-F energy subscale , P=.02 ) . Analysis of the regression slopes by means of hierarchical linear modeling demonstrated a significantly greater rate of improvement in PFS total scores among patients receiving psychostimulants compared with the placebo group ( P=.02 ) . There were no significant differences in the efficacy between methlypheni date and pemoline on any outcome measure studied . Improvement in fatigue was also significantly correlated with improvement in measures of depression , psychological distress , and overall quality of life . Severe side effects were relatively uncommon among this sample , and only hyperactivity or jitteriness occurred significantly more often among subjects receiving active medication . CONCLUSIONS Many patients with HIV- and acquired immunodeficiency syndrome-unrelated fatigue respond favorably to treatment with methylpheni date or pemoline . Both psychostimulants appear to be equally effective and significantly superior to placebo in decreasing fatigue severity with minimal side effects . Moreover , improvement of fatigue was significantly associated with improved quality of life and decreased levels of depression and psychological distress 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 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 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 Although much has been learned about the complication of fatigue during breast cancer treatment , the possibility that there are differences across treatment modalities in breast cancer patients ' experience of fatigue has not yet been established . In this study , fatigue was assessed in 134 women receiving chemotherapy and radiotherapy or radiotherapy only for early stage breast cancer . Comparisons of fatigue during initial treatment indicated that women who received chemotherapy reported greater fatigue severity and disruptiveness than women receiving radiotherapy . Women not pre-treated with chemotherapy experienced increased fatigue over the course of radiotherapy . Results confirmed predictions that fatigue in women with early stage breast cancer differs as a function of the type of treatment and sequencing of treatment . Findings indicating increases in fatigue during radiotherapy only among women not pretreated with chemotherapy suggest a response shift , or a change in internal st and ards , in women 's perceptions of fatigue as a function of prior chemotherapy treatment 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 This study evaluated a supportive intervention for fatigue in patients undergoing chemotherapy . One hundred three chemotherapy-naïve patients were recruited , stratified by treatment regimen , and r and omly allocated to intervention or usual care . The intervention was conducted over three months . Recipients were provided with an investigator- design ed information pack and Fatigue Diary that they completed during the week following each treatment . Additionally , support nurses visited them monthly at home . They assessed fatigue , provided psychological support , and coached participants in self-care . The intervention group reported significantly less fatigue ( P < 0.05 ) , lower associated distress ( P < 0.05 ) , and less impact of fatigue on valued pastimes ( P < 0.05 ) than the control group . Further , they reported significantly less anxiety ( P < 0.05 ) and depression ( P < 0.05 ) and displayed more adaptive coping ( P < 0.05 ) . The intervention enabled patients to adapt to living with fatigue and contributed to their psychological/emotional well-being and ability to cope with their illness and treatment Abstract In a study concerning a group of cancer patients undergoing radiotherapy  three research questions were addressed . ( 1 ) Is fatigue a valid criterion for depression in these somatically ill patients ? ( 2 ) What is the ' cause- and -effect ' relation between fatigue and depression ? ( 3 ) To what extent are fatigue and depression related to patients ' quality of life . A heterogeneous sample of cancer patients ( n = 250 ) were interviewed before treatment , 2 weeks after treatment and 9 months later . Fatigue was measured using the  MFI  , a self-report instrument covering five dimensions of fatigue . Depression was assessed with the non-somatic items of the CES-D. Quality of life had to be indicated on a Cantrill ladder . Fatigue and depression do not follow the same course over time . Just after radiotherapy , fatigue had either increased or remained stable , depending on the dimension under consideration . Depression , in contrast , decreased . Nine months later fatigue had decreased , whereas levels of depression remained stable . Concurrent relations between fatigue and depression were mostly moderate . There was no strong evidence for a cause- and -effect relationship between depression and fatigue . Depression showed highest concurrent relationships with quality of life , especially before treatment . Prospect ively , depression and the dimension of physical fatigue were the main predictors for quality of life . Fatigue is not a valid criterion for depression in these patients . Nor is there a strong cause- and -effect relationship . Both depression and physical fatigue are relevant to patients ' quality of life Anaemia is a common haematologic disorder in patients with cancer and has a multifactorial aetiology , including the effects of the malignancy itself and residual effects from previous therapy . Novel erythropoiesis stimulating protein ( NESP , darbepoetin alfa ) , a protein with additional sialic acid compared with erythropoietin ( EPO ) , stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin ( rHuEPO ) but it is biochemically distinct . NESP , with its approximately 3-fold greater serum half-life , can maintain haemoglobin levels as effectively as rHuEPO in anaemic patients with chronic renal failure and do so with less frequent dosing . We investigated the ability of NESP to safely increase haemoglobin levels of anaemic patients with non-myeloid malignancies not receiving chemotherapy .  NESP was administered under the supervision of a physician at doses of 0.5 , 1.0 , 2.25 or 4.5 mcg kg–1wk–1for a maximum of 12 weeks . This report includes 89 patients completing the study by November 2000 .  NESP was well tolerated , with no reported dose-limiting toxicities or treatment-related severe adverse events . Increasing doses of NESP corresponded with increased efficacy . The percentage ( 95 % confidence interval ) of patients responding ranged from 61 % ( 42 % , 77 % ) in the 1.0 mcg kg–1wk–1group to 83 % ( 65 % , 94 % ) in the 4.5 mcg kg–1wk–1group . © 2001 Cancer Research In part A of this study , patients were r and omised to cohorts receiving darbepoetin alfa  at doses of 0.5 to 8.0 m.c.g . kg−1 wk−1 or to a control group receiving epoetin alfa  at an initial dose of 150 U kg−1 three times weekly . In part B , the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g . kg−1 every 2 weeks or epoetin alfa , initial dose 40 000 U wk−1 . Safety was assessed by adverse events , changes in blood pressure , and formation of antibodies to darbepoetin alfa . Efficacy was assessed by several haematologic endpoints , including change in haemoglobin from baseline . The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa . No relationship between the rapidity of haemoglobin response and any adverse event was observed . No antibodies to darbepoetin alfa were detected . Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response . The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks . Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy PURPOSE To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer . METHODS A total of 84 patients with advanced , solid tumours not responsive to hormone therapy were enrolled in this double-blind , crossover study . During phase 1 , patients were r and omly assigned to receive megestrol acetate ( 160 mg 3 times daily ) for 10 days or placebo . During phase 2 , after a 2-day washout period , patients received the alternate treatment for 10 days . Patients underwent daily assessment s of activity , nausea , appetite and well-being by means of a visual analogue scale ( VAS ) . In addition , nutritional status ( weight , tricep skinfold measure , arm muscle circumference ) , energy intake , fatigue ( Piper Fatigue Scale ) and quality of life ( Functional Living Index-Cancer [ FLIC ] ) were assessed . RESULTS Among the 53 evaluable patients  megestrol acetate result ed in a significant improvement in appetite ( p = 0.005 ) , activity ( p = 0.007 ) and well-being ( p = 0.03 ) . There was no significant change in the intensity of nausea , nutritional parameters , energy intake or FLIC scores . There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score . Upon completion of the study , while still blind to the treatment condition , 30 patients indicated that they felt better overall after megestrol , 15 said they felt better after placebo , and 10 indicated no preference ( p = 0.001 ) . CONCLUSION Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported . The effects are not secondary to nutritional changes . The FLIC quality -of-life question naire was unable to detect these changes 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 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 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 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 The aim of this study was to evaluate whether diagnostic criteria for cancer-related fatigue syndrome ( CRFS ) could be rigorously applied to cancer in patients , and to explore the relationship between subjective fatigue and objective measures of physical activity , sleep , and circadian rhythm . Female cancer patients ( n=25 ) and a comparison group of subjects without cancer ( n=25 ) were studied . Study participants completed a structured interview for CRFS and question naires relating to  fatigue , psychological symptoms , and quality of life ( QoL ) . Wrist actigraphs worn for 72 hours were used as an objective measure of activity , sleep , and circadian rhythm . Compared to controls , cancer patients were more fatigued , had worse sleep quality , more disrupted circadian rhythms , lower daytime activity levels , and worse QoL. After exclusion of subjects with " probable " mood disorders , the prevalence of CRFS was 56 % . Fatigue severity among the cancer patients was significantly correlated with low QoL , depression , constipation , and decreased self-reported physical functioning . It can be concluded that the diagnostic criteria for CRFS can be applied to cancer in patients but strict application requires a rigorous assessment of psychiatric comorbidity . Despite cancer in patients having greater impairments of sleep and circadian rhythm , it was found that fatigue severity did not appear to be related to these impairments PURPOSE Use a proposed case-definition approach to identify the prevalence of  cancer-related fatigue ( CRF )  , demographic , clinical and psychosocial predictors of subsequent CRF , and psychosocial factors associated with concurrent CRF . PATIENTS AND METHODS Women ( n = 288 ) undergoing adjuvant therapy for early-stage breast cancer were recruited from two outpatient clinics . Women completed a baseline assessment before adjuvant therapy and a post-treatment assessment at the conclusion of an initial course of adjuvant chemotherapy or radiotherapy . At both assessment s , women completed a  clinical interview  and measures of  fatigue , distress , coping , and quality of life ( QOL ) . The clinical interview consisted of modules from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition ( DSM-IV ) and a diagnostic interview to identify cases of CRF . RESULTS CRF prevalence at the baseline and post-treatment assessment s was 10 % and 26 % , respectively . Multivariate analyses identified factors prospect ively associated with greater risk for CRF at the post-treatment assessment , including receipt of adjuvant chemotherapy and a tendency to catastrophize in response to fatigue . Patients with and without CRF differed on a host of concurrent measures of fatigue , depression , functioning , and QOL with mean effect sizes in the range of 1.0 st and ard deviation . CONCLUSION CRF is a clinical syndrome experienced before and during adjuvant therapy for breast cancer . Results suggest CRF has a multifactorial etiology and support use of the proposed case definition approach to defining CRF . Future research is necessary to determine the scientific value of these criteria for underst and ing the etiology and management of fatigue in the oncology setting 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 PURPOSE Previous trials have suggested a quality -of-life ( QOL ) improvement for anemic cancer patients treated with erythropoietin , but few used QOL as the primary outcome . We design ed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung ( NSCLC ) . PATIENTS AND METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was conducted . The proposed sample size was 300 patients . Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin ( Hgb ) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo , targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks . RESULTS Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been r and omly assigned ( 33 to the active arm and 37 to the placebo arm ) . This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial ( 63 v 129 days ; hazard ratio , 1.84 ; P = .04 ) . The Steering Committee closed the trial . Patient numbers compromised the interpretation of the QOL analysis , but a positive Hgb response was noted with epoetin alfa treatment . CONCLUSION An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa . Although infrequent , other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely 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 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 Objectives : Platinum compounds are commonly associated with significant anemia .  Erythropoietin administration has been found effective in correcting anemia in patients with solid tumors receiving chemotherapy . We conducted a r and omized , open label study to assess the efficacy of erythropoietin in preventing transfusions and significant anemia ( hemoglobin < 10 g/dl ) in patients with solid tumors receiving platinum-based chemotherapy . Methods : One hundred forty-four patients with hemoglobin < 13 g/dl were included in this study ( 72 in each arm ) . Patients in the treatment arm received 10,000 U of recombinant human erythropoietin ( rHuEPO ) thrice weekly s.c . during platinum-based chemotherapy , while patients in the control arm received no treatment . Results : All patients were evaluable for efficacy . Transfusions were reduced by the administration of rHuEPO ( 15.3 vs. 33.3 % , p = 0.019 ) , and fewer patients developed significant anemia ( 16.6 vs. 45.8 % , p < 0.0001 ) . Subgroup analysis showed that patients with observed to predicted ( O/P ) serum erythropoietin levels ≤0.9 and responders to chemotherapy benefited from erythropoietin administration in contrast to patients with O/P > 0.9 or non-responders . Conclusions : rHuEPO at a dose of 10,000 U thrice weekly prevents transfusions and development of significant anemia in patients with solid tumors receiving platinum-based chemotherapy PURPOSE Epoetin alfa administered at 40,000 U once weekly ( qw ) to anemic cancer patients receiving chemotherapy increases hemoglobin levels , improves quality of life ( QOL ) , and reduces transfusions . The benefit of epoetin alfa in maintaining hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not been evaluated . METHODS Breast cancer patients ( N = 354 ) receiving chemotherapy  were r and omly assigned in 1:1 ratio to epoetin alfa ( 40,000 U qw ) or st and ard of care ( SOC ) .  QOL was assessed at baseline and week 12 . Hemoglobin responses , transfusion requirements , and prognostic factors for responses were measured . RESULTS At week 12 , Functional Assessment of Cancer Therapy-Anemia ( FACT-An ; mean , 2.16 + /- 12.84 for epoetin alfa v -4.43 + /- 13.42 for SOC ) and FACT-An fatigue ( mean , 1.85 + /- 10.52 for epoetin alfa v -3.55 + /- 11.14 for SOC ) change scores were significantly higher in the epoetin alfa group ( P < .0001 ) . Hemoglobin responses defined as mean hemoglobin > or = 12 g/dL or a > or = 2 g/dL increase compared with baseline were significantly higher in the epoetin alfa group versus SOC : 52.0 % v 5.1 % and 65.7 % v 6.3 % , respectively ( P < .0001 for both comparisons ) . Percentage transfused was significantly lower in the epoetin alfa group compared with SOC ( 8.6 % v 22.9 % ) . More than 90 % of patients did not require a dose increase and 28.7 % had a dose reduction . CONCLUSION Epoetin alfa administered at 40,000 U qw is effective in improving QOL , maintaining hemoglobin level , and reducing transfusion requirements  in breast cancer patients . The high effectiveness observed could be attributed in part to early treatment with epoetin alfa 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
BACKGROUND Cancer-related fatigue is an important clinical problem .
It is common , distressing , and often difficult to treat .
There is a role for drug treatment of cancer-related fatigue , but no consensus has been reached on which drugs are useful .
This systematic review and meta- analysis aims to review the available evidence and make recommendations for practice and research .