Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Yoga's impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. Age- and sex-standardised prevalence rates of fatigue in a large hospital-based sample of cancer patients Fatigue and physical activity in older patients with cancer: a six-month follow-up study. Relationship Between Age and Symptoms of Pain and Fatigue in Adults Undergoing Treatment for Cancer Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan‐based chemotherapy Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. Fatigue during breast radiotherapy and its relationship to biological factors.
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 Flu-like symptoms are common , early transient side effects of paclitaxel chemotherapy . We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment . The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta , IL-6 , IL-8 , IL-10 , IL-12 , and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms . METHODS Ninety patients with breast cancer were included ; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC ( 5-FU , doxorubicin , cyclophosphamide ) chemotherapy . Fifteen healthy volunteers were included as controls .  Cytokines and symptoms were measured before starting therapy , on day 3 and on the last day of one treatment cycle . RESULTS At baseline , all subjects had measurable levels of IL-8 but only 49 % had IL-12 , 45 % had IL-10 , 32 % had IL-6 , and 21 % had IL-1beta or TNF-alpha in their plasma . There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers . Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients . In the every 3-week paclitaxel group , IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline . Fatigue and flu-like symptoms were also worse on day 3 . In the weekly paclitaxel group , increase in IL-10 level correlated positively with joint pain ( p=0.003 ) . In the every 3-week paclitaxel group , increase in IL-8 level correlated positively with flu-like symptom ( p=0.008 ) . In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly . CONCLUSIONS Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and IL-6 in the plasma . These changes correlate with joint pain and flu-like symptoms PURPOSE To evaluate yoga 's impact on inflammation , mood , and fatigue . PATIENTS AND METHODS A r and omized controlled 3-month trial was conducted with two post-treatment assessment s of 200 breast cancer survivors assigned to either 12 weeks of 90-minute twice per week hatha yoga classes or a wait-list control . The main outcome measures were lipopolysaccharide-stimulated production of proinflammatory cytokines interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-α ) , and interleukin-1β ( IL-1β ) , and scores on the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) , the vitality scale from the Medical Outcomes Study 36-item Short Form ( SF-36 ) , and the Center for Epidemiological Studies -Depression ( CES-D ) scale . RESULTS Immediately post-treatment , fatigue was not lower ( P > .05 ) but vitality was higher ( P = .01 ) in the yoga group compared with the control group . At 3 months post-treatment , fatigue was lower in the yoga group ( P = .002 ) , vitality was higher ( P = .01 ) , and IL-6 ( P = .027 ) , TNF-α ( P = .027 ) , and IL-1β ( P = .037 ) were lower for yoga participants compared with the control group . Groups did not differ on depression at either time ( P > .2 ) . Planned secondary analyses showed that the frequency of yoga practice had stronger associations with fatigue at both post-treatment visits ( P = .019 ; P < .001 ) , as well as vitality ( P = .016 ; P = .0045 ) , but not depression ( P > .05 ) than simple group assignment ; more frequent practice produced larger changes . At 3 months post-treatment , increasing yoga practice also led to a decrease in IL-6 ( P = .01 ) and IL-1β ( P = .03 ) production but not in TNF-α production ( P > .05 ) . CONCLUSION Chronic inflammation may fuel declines in physical function leading to frailty and disability . If yoga dampens or limits both fatigue and inflammation , then regular practice could have substantial health benefits Background : The aim of this longitudinal study was to determine age- and sex-st and ardised prevalence rates of cancer-related fatigue in different groups of patients . Methods : This was a prospect i ve study in a cohort of N=1494 cancer patients investigating fatigue at three time points t1–t3 ( t1 : admission to hospital , t2 : discharge , t3 : half a year after t1 ) .  Fatigue was measured with the  Multidimensional Fatigue Inventory . Age- and sex-adjusted norms were derived from a representative community sample of N=2037 , using a cutoff at the 75th percentile . Results : At admission to the hospital , 32 % of the patients were classified as fatigued . At discharge , the overall prevalence rate was 40 % , and at half a year after t1 , prevalence was 34 % . Fatigue prevalence rates differed according to tumour stage , site , age , and sex of the patients . Conclusion : The prevalence rates provided by this study can be used for the planning of research and clinical routine PURPOSE / OBJECTIVES To determine the relationship between fatigue and physical activity in older patients with cancer . DESIGN Targeted analysis using data from a prospect i ve longitudinal study . SETTING A cancer care facility in southeastern Ontario , Canada . SAMPLE 440 patients , aged 65 years and older , seeking consultation for cancer treatment at a regional cancer clinic for lymphoma or leukemia or lung , breast , genitourinary , head or neck , gastrointestinal , or skin cancers . METHODS Self-report question naires were mailed to consenting participants and completed at baseline and three and six months after consultation for cancer treatment . MAIN RESEARCH VARIABLES Participants rated fatigue and physical activity and reported comorbidities and personal demographic characteristics . Clinical measures of disease and treatment factors were obtained through chart abstract ion . FINDINGS Fatigue was the most prevalent symptom reported . Higher fatigue was associated with lower physical activity levels . Physical activity level significantly predicted fatigue level , regardless of age . CONCLUSIONS Physical activity level is a modifiable factor significantly predicting cancer-related fatigue at three and six months following consultation for cancer treatment . The results suggest that physical activity may reduce fatigue in older patients with cancer . IMPLICATION S FOR NURSING Physical activity interventions should be developed and tested in older patients with cancer Background : Pain and fatigue are 2 of the most common symptoms experienced by individuals undergoing treatment for cancer . It has been hypothesized that older adults experience lower levels of severity and interference from pain and fatigue when compared with younger adults . Objective : The purpose of this study was to identify how pain and fatigue , severity , and interference may vary between younger and older adults undergoing cancer treatment over time . Methods : This study is a secondary analysis of data of 2 different r and omized controlled trials that examined the symptom experience in adults undergoing treatment for cancer .  A linear mixed model analysis was used to determine the differences based on age across 6 contacts over 8 weeks . Results : Results indicate that pain severity is significantly ( P < .01 ) related to age . Age was not found to be significantly related to the level of interference associated with pain or the severity or interference associated with fatigue . Conclusion : Symptoms of pain and fatigue are prevalent across age groups and will vary across time . Older and younger adults do not necessarily experience symptoms differently . Interference associated with pain and fatigue impacts all age groups ; interference may not be directly related to the level of severity . Implication s for Practice : This study highlights the importance of assessing both severity and interference associated with symptoms in all adults undergoing treatment for cancer . Further research is needed to better underst and the relationship between age and symptoms in individuals undergoing treatment for cancer Brain gray matter alterations have been reported in cross-sectional magnetic resonance imaging ( MRI ) studies of breast cancer patients after cancer treatment . Here we report the first prospect i ve MRI study of women undergoing treatment for breast cancer , with or without chemotherapy , as well as healthy controls . We hypothesized that chemotherapy-associated changes in gray matter density would be detectable 1 month after treatment , with partial recovery 1 year later . Participants included breast cancer patients treated with ( CTx+ , N = 17 ) or without ( CTx− , N = 12 ) chemotherapy and matched healthy controls ( N = 18 ) .  MRI scans were acquired at baseline ( after surgery but before radiation , chemotherapy , and /or anti-estrogen treatment ) , 1 month after completion of chemotherapy ( M1 ) , and 1 year later ( Y1 ) . Voxel-based morphometry ( VBM ) was used to evaluate gray matter density differences between groups and over time . There were no between-group gray matter differences at baseline . Group-by-time interactions showed declines from baseline to M1 in both cancer groups relative to controls . Within-group analyses indicated that at M1 relative to baseline the CTx+ group had decreased gray matter density in bilateral frontal , temporal , and cerebellar regions and right thalamus . Recovery was seen at Y1 in some regions , although persistent decreases were also apparent . No significant within-group changes were found in the CTx− or control groups . Findings were not attributable to recency of cancer surgery , disease stage , psychiatric symptoms , psychotropic medication use , or hormonal treatment status . This study is the first to use a prospect i ve , longitudinal approach to document decreased brain gray matter density shortly after breast cancer chemotherapy and its course of recovery over time . These gray matter alterations appear primarily related to the effects of chemotherapy , rather than solely reflecting host factors , the cancer disease process , or effects of other cancer treatments 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 In the current Phase II study , the authors evaluated the association between genomic polymorphic variants in uridine diphosphate glucuronosyl transferase ( UGT1A1 ) , methylenetetrahydrofolate reductase ( MTHFR ) , and thymidylate synthase ( TS ) genes , and the incidence of the adverse effects of irinotecan and raltitrexed  in previously heavily treated patients with metastatic colorectal carcinoma Some breast cancer survivors experience cognitive decline following chemotherapy . We prospect ively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide , thiotepa , and carboplatin ( CTC group ; n = 28 ) or st and ard-dose chemotherapy with 5-fluorouracil , epirubicin , and cyclophosphamide ( FEC group ; n = 39 ) ; stage-I breast cancer patients who had received no systemic chemotherapy ( no-CT group ; n = 57 ) ; and healthy control subjects ( n = 60 ) . All patients underwent  neuropsychologic testing  before and 6 months after treatment ( 12-month interval ) ; control subjects underwent repeated testing over a 6-month interval . No differences in cognitive functioning between the four groups were observed at the first assessment . More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time ( 25 % versus 6.7 % ; odds ratio [ OR ] = 5.3 , 95 % confidence interval [ CI ] = 1.3 to 21.2 , P = .02 ) . No such difference was observed for the FEC or the no-CT groups ( FEC versus control : OR = 2.2 , 95 % CI = 0.5 to 9.1 , P = .27 ; no-CT versus Control : OR = 2.2 , 95 % CI = 0.6 to 8.0 ; P = .21 ) . Some cytotoxic treatment for breast cancer affects cognition in a subset of women INTRODUCTION Fatigue is commonly reported in patients receiving radiotherapy for breast conservation , but the underlying mechanisms remain unclear . METHODS Patients with early breast cancer participating in a prospect i ve study of the impact of inflammatory processes on early and delayed breast morbidity were assessed for fatigue levels using the Functional Assessment of Cancer Therapy ( FACT ) fatigue subscale before and at intervals during and after radiotherapy . Blood for analysis of a variety of circulating cytokines , coagulation factors , peripheral blood indices and biochemical factors was collected at the same time points . RESULTS Fifty-two eligible patients were assessed . Twenty-one patients ( 43 % ) developed significant fatigue during radiotherapy , whereas 28 ( 54 % ) developed minimal or no fatigue . Fatigue appeared to plateau between week 4 of treatment and 2 weeks after treatment . The fatigue was beginning to settle by 6 weeks after treatment . Significant fatigue was predicted by a higher baseline fatigue score , red cell count , neutrophil count , and D-dimer level . Baseline fatigue correlated with higher body mass index , C-reactive protein , soluble thrombomodulin , tissue plasminogen activator , von Willebr and factor antigen , interleukin-6 , ICAM-1 , hemoglobin and red cell , monocyte , and neutrophil counts . There were also significant correlations between body mass index and tissue plasminogen activator , C-reactive protein , interleukin-6 , ICAM-1 , and red cell count . After these factors were controlled for , baseline fatigue was seen to be associated with higher body mass index , soluble thrombomodulin , tissue plasminogen activator , von Willebr and factor antigen , monocyte count , and neutrophil count . Multiple logistic regression procedures indicated that the most predictive factors for fatigue during radiotherapy were higher baseline fatigue level and higher baseline neutrophil and red cell counts . CONCLUSION This study has shown that significant fatigue is common in patients receiving breast irradiation and is precipitated during radiotherapy in some patients but not others . The factors shown to be associated with fatigue in this study will be helpful in shaping future studies
Purpose Underst and ing the etiology of cancer-related fatigue ( CRF ) is critical to identify targets to develop therapies to reduce CRF burden .
The goal of this systematic review was to exp and on the initial work by the National Cancer Institute CRF Working Group to underst and the state of the science related to the biology of CRF and , specifically , to evaluate studies that examined the relationships between biomarkers and CRF and to develop an etiologic model of CRF to guide research ers on pathways to explore or therapeutic targets to investigate .