Multidimensional Fatigue Symptom Inventory-Short Form Research Articles

Cancer survivors' exercise barriers, facilitators and preferences in the context of fatigue, quality of life and physical activity participation: a questionnaire–survey

To investigate the exercise barriers, facilitators and preferences of a mixed sample of cancer survivors as well as fatigue levels, quality of life (QoL) and the frequency and intensity of exercise that cancer survivors typically engage in. An anonymous, postal questionnaire-survey with a convenience sample of 975 cancer survivors was used. Standardised measures were used to establish fatigue (Multidimensional Fatigue Symptom Inventory-Short Form), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30), exercise frequency and intensity (Leisure Score Index). A 52.3% response rate (n = 456) was achieved. A total of 76.0% were female, with stage I (18.3%) or stage II (21.0%) breast cancer (64.4%), and 62.3% were ≥ 3 years post treatment. A total of 73.5% reported fatigue with 57.2% experiencing fatigue on a daily basis. A total of 68.1% had never been given any advice on how to manage fatigue. A total of 9.4% reported to engage in strenuous physical activity, 43.5% in moderate physical activity and 65.5% in mild physical activity. Respondents experienced difficulties with emotional, cognitive and social functioning and the symptoms of fatigue, insomnia and pain. Barriers that interfered with exercise 'often/very often' were mainly related to respondents' health and environmental factors. A total of 50.2% were interested in exercise and 52.5% felt able to exercise. Exercise facilitators, preferences and motivators provide some insight into cancer survivors' needs in terms of becoming more physically active. Although cancer survivors continue to experience fatigue and QoL issues long after treatment completion, over half are willing and feel able to participate in exercise. Exercise barriers were mainly health related or environmental issues, however, the main barriers reported were those that had the potential to be alleviated by exercise.

Absence of neuropsychological impairment in hyperammonaemia in healthy young adults; possible synergism in development of hepatic encephalopathy (HE) symptoms?

The aetiology of minimal hepatic encephalopathy (mHE) remains unclear. It is generally accepted that hyperammonaemia plays a major role, however there are a multitude of metabolic perturbations present. To determine the contribution of hyperammonaemia to mHE symptom development, ten healthy males (Age:25 ± 5yrs, BM:76.3 ± 7.1kg, Height:178.6 ± 4.5cm, mean ± SD) received two 4h intravenous infusions of either a 2% ammonium chloride solution (AMM) or a placebo (PLA;0.9% sodium chloride) using a double blind cross-over design. Sensations of fatigue were measured at baseline, 2 and 4h using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) questionnaire. Learning & memory, motor control and cognition were assessed using Rey's Auditory Verbal Learning Test (AVL), Continuous Compensatory Tracking (COMPTRACK) Task and Inhibitory Control Test (ICT) respectively. Arterialised venous blood samples were collected every hour, and analysed for ammonia concentration. There was a significantly higher plasma ammonia concentration in the AMM trial than the PLA trial at every time point during the infusion, peaking at 2h (57 ± 4μmol/L PLA, 225 ± 14μmol/L AMM; p < 0.05). At 2h there were significantly higher sensations of general fatigue (Z = -2.527, p = 0.008, 2 tailed) and physical fatigue (Z = -2.156, p = 0.027, 2 tailed), and lower sensations of vigour (Z = -2.456, p = 0.012, 2 tailed) for the AMM trial. There were no significant effects on the performance of the psychological tasks. These results demonstrate that hyperammonaemia in the absence of other complications induces significant sensations of fatigue but does not cause the typically observed performance impairment in individuals with mHE. Supporting the hypothesis for synergism between ammonia and other co-factors in mHE.

Child maltreatment and breast cancer survivors: Social support makes a difference for quality of life, fatigue and cancer stress

PurposeTo identify how child maltreatment is associated with quality of life (QOL) among breast cancer survivors. Patients and methodsOne hundred and thirty two women who had completed treatment for stage 0-IIIA breast cancer within the past 2years (except for tamoxifen/aromatase inhibitors) and were at least 2months post surgery, radiation, or chemotherapy completed questionnaires including the Childhood Trauma Questionnaire, the Impact of Events Scale, the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and the Fact-B breast cancer quality of life questionnaire. ResultsWomen who were abused or neglected as children reported more cancer-related psychological distress, more fatigue and poorer physical, emotional, functional and breast cancer-specific well-being after treatment. These relations were partially explained by the fact that breast cancer survivors reported receiving less support as adults. ConclusionThe findings suggest that child maltreatment is an important predictor of QOL among breast cancer survivors. One reason why this association exists is because those who are maltreated as children report less support as adults. A better understanding of how child maltreatment contributes to breast cancer survivor QOL will help in tailoring and, therefore, enhancing the efficacy of interventions aimed at improving QOL.

A randomised controlled trial testing the feasibility and efficacy of a physical activity behavioural change intervention in managing fatigue with gynaecological cancer survivors

Objective To determine the feasibility and efficacy of a physical activity behavioural change intervention in managing cancer-related fatigue among gynaecological cancer survivors during and post anti-cancer treatments. Methods A two arm, single blind, randomised controlled trial was conducted within the Northern Ireland regional Cancer Centre. Thirty three sedentary gynaecological cancer survivors (stage I–III; ≤ 3 years post diagnosis), experiencing cancer-related fatigue (mild–severe) took part. Participants were randomly assigned to a behavioural change, moderate intensity physical activity intervention (n = 16) or a Contact Control group (n = 17). The primary outcome was fatigue (Multidimensional Fatigue Symptom Inventory—Short Form and Functional Assessment in Chronic Illness Therapy—Fatigue subscale). Secondary outcomes included quality of life, physical functioning, positive and negative affect, depression, body composition, sleep dysfunction and self-reported physical activity. Feasibility was assessed based on the recruitment rate, programme and physical activity adherence and participants' programme evaluation, including optional focus groups (n = 16). Results Twenty five percent of eligible women took part (33/134). Participants were 8.7 (SD = 9.1) months post diagnosis, with a mean age of 53 (SD = 10.3) years. The majority of the sample had a diagnosis of ovarian (n = 12) or endometrial cancer (n = 11). Significant differences favouring the intervention group were observed for fatigue at 12 weeks and 6 months follow-up (12 week: mean difference = −11.06; 95% confidence interval (CI) = −21.89 to − 0.23; effect size (d) = 0.13; p = 0.046; 6 month: mean difference = −19.48; 95% CI = − 19.67 to − 19.15; effect size (d) = 0.20; p = 0.01). A mean of 10 calls (SD = 1.2 calls) were delivered to the Physical Activity Group, and 10 (SD = 1.6 calls) to the CC group. The intervention was positively perceived based on exit questionnaire and focus group findings. Conclusions A physical activity behavioural change intervention for gynaecological cancer survivors is feasible in terms of participants' programme adherence and evaluation, and the intervention demonstrates improvements in fatigue. However, confirmation in the form of a larger fully powered RCT is warranted.

Reliability and validity of a Chinese version of the Multidimensional Fatigue Symptom Inventory‐Short Form (MFSI‐SF‐C)

To examine the psychometric properties of the Chinese version of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF-C) for use in Chinese-speaking countries. The assessment of fatigue is a challenging task for most researchers because culture may influence perceptions of meaning of fatigue. The lack of examination of the psychometric properties of the fatigue measures across studies limits the scientific rigour for generating additional research on the concept of 'fatigue.' A cross-sectional study. The study recruited 107 cancer inpatients from two medical centres in Taiwan. The MFSI-SF-C was examined using a two step process: (1) Translation and back-translation of the instrument; and (2) Examination of internal consistency reliability, test-retest reliability, content validity and construct validity. The results showed that the Cronbach's α of MFSI-SF-C total scale and subscales ranged between 0·83-0·92. The content validity index was 0·93. The difference between the fatigue of cancer patients and the comparison group of healthy people in the community was significant. The results demonstrated good convergent validity when comparing fatigue with depression and quality of life. Factor analysis confirmed the four dimensions of fatigue: physical, emotional, mental and vigour. It showed moderate intercorrelation between subscales and high factor loadings also helped to clarify the psychometric meaning. The reliability and validity information presented in this article support the use of the Chinese version of the MFSI-SF as a research instrument for measuring fatigue in Chinese populations. This study also provides evidence that the MFSI-SF possesses robust psychometric properties. The MFSI-SF-C is an effective and comprehensive tool for measuring fatigue in Chinese patients with cancer.

Effects of continuous positive airway pressure on fatigue and sleepiness in patients with obstructive sleep apnea: data from a randomized controlled trial.

Complaints of fatigue are frequent in patients with obstructive sleep apnea (OSA); however, the impact of continuous positive airway pressure (CPAP) on fatigue remains unclear. Fifty-nine men and women with OSA were randomly assigned to therapeutic or placebo CPAP in a double-blind fashion for a 3-week intervention period. Four outcome measures were assessed: (1) fatigue/vigor measured with the Multidimensional Fatigue Symptom Inventory--Short Form (MFSI-sf), the (2) fatigue and (3) vigor subscales of the Profile of Mood States--Short Form (POMS), and (4) the Epworth Sleepiness Scale (ESS). Data were analyzed using repeated-measures analysis of variance. Compared with patients receiving placebo CPAP, those patients treated with therapeutic CPAP showed significant reductions in the apnea-hypopnea index, as well as decreases in both measures of fatigue and increases in vigor (P values < 0.05). The beneficial effect of therapeutic treatment was most pronounced in patients with high levels of fatigue at study onset. Significant treatment effects in sleepiness scores were not observed in the entire sample (P > 0.05); however, in a subset of patients with excessive sleepiness at the onset of treatment, ESS scores were significantly reduced with use of therapeutic CPAP (P < 0.05). Results suggest that 3 weeks of therapeutic CPAP significantly reduced fatigue and increased energy in patients with OSA. Therapeutic CPAP significantly reduced daytime sleepiness in patients who reported excessive sleepiness at the onset of treatment.

Number of Lapses during the Psychomotor Vigilance Task as an Objective Measure of Fatigue

This study examined how well the Psychomotor Vigilance Task (PVT) performance was related to subjective measures of fatigue. In order to study subjects presenting with a wide range of fatigue symptoms, we studied healthy individuals as well as patients with varying severity of obstructive sleep apnea. We also examined if the PVT/fatigue relationship could be influenced by depressive symptoms. Forty-eight participants had their sleep monitored with polysomnography. Fatigue was assessed by Multidimensional Fatigue Symptom Inventory-short form (MFSI-sf). Depressed mood was assessed by the Center for Epidemiologic Studies-Depression (CES-D) Scale. After sleep monitoring and psychological assessments, the 10-minute PVT was administered. The main outcome variable was the PVT lapse count. Simple correlations and hierarchical linear regression were used to examine the association between age, body mass index (BMI), sleep variables, apnea hypopnea index (AHI), oxygen desaturation index (ODI), CES-D, fatigue, and PVT. The PVT lapse count was significantly associated with MFSI-sf physical fatigue (r = 0.324, p = 0.025). In hierarchical regression (full model R2 = 0.256, p = 0.048), higher BMI (p = 0.038), and higher MFSI-sf physical fatigue (p= 0.040) were independent predictors of the PVT lapse count. Age, AHI, ODI, and CES-D were unrelated to the PVT lapse count. In conclusion, the findings suggest that even after controlling for age, BMI, depression, and apnea severity, physical fatigue is associated with the PVT lapse.

Fatigue in Gynecological Cancer Patients During and After Anticancer Treatment

Context Research has indicated that individuals with gynecological cancer experience severe fatigue. Objectives This longitudinal survey aimed to analyze the fatigue experienced over the course of one year by a gynecological cancer population, to determine if the fatigue was more severe than that reported by females without cancer, and to identify variables associated with cancer-related fatigue (CRF). Methods Data were collected over a 12-month period before, during, and after anticancer treatment. Fatigue was assessed using the Multidimensional Fatigue Symptom Inventory-Short Form. Participants with cancer also completed the Rotterdam Symptom Checklist. Results Sixty-five cancer patients (mean age = 57.4 years, standard deviation [SD] = 13.9) and 60 control subjects (mean age = 55.4 years, SD = 13.6) participated. Descriptive analysis and repeated measurements modeling indicated that the cancer participants reported worse fatigue than the noncancer individuals before, during, and after anticancer treatment ( P < 0.001) and that the level of fatigue in persons with cancer changed with time ( P = 0.02). A forward stepwise regression demonstrated that psychological distress level was the only independent predictor of CRF during anticancer treatment ( P < 0.00), explaining 44% of the variance in fatigue. After treatment, both psychological distress level ( P < 0.00) and physical symptom distress ( P = 0.03) were independent predictors of fatigue, accounting for 81% of the variance. Conclusion Psychological distress level is an important indicator of CRF in gynecological cancer. Interventions focused on the reduction of psychological distress may help alleviate CRF.

The moderating role of personal mastery on the relationship between caregiving status and multiple dimensions of fatigue

A substantial proportion of chronically-stressed spousal dementia caregivers report fatigue. The objective of this study was to examine whether personal mastery moderates the relationship between caregiving status (caregiver/non-caregiver) and multiple dimensions of fatigue. Seventy-three elderly Alzheimer's caregivers and 41 elderly non-caregivers completed the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and questionnaires assessing mastery. Regression analyses indicated that global fatigue was significantly higher for caregivers (M = 38.0 +/- 21.0) compared to non-caregivers (M = 18.2 +/- 10.4). However, personal mastery moderated the relation between caregiving status and global fatigue (t = -2.03, df = 107, p = 0.045), such that for those with low mastery, caregivers' fatigue scores were 18.1 points higher than non-caregivers, and for those with high mastery, this difference was only 7.5 points. For specific dimensions of fatigue, mastery moderated the relations between caregiving status and both emotional (t = -2.01, df = 107, p = 0.047) and physical (t = -2.51, df = 107, p = 0.014) fatigue. Specifically, association between caregiving status and emotional fatigue was greater when mastery was low than when mastery was high. Caregiving status was significantly associated with physical fatigue when mastery was low, but not when mastery was high. Significant main effects were found between mastery and general fatigue and vigor. Given the proportion of fatigued caregivers and the impact fatigue has on health; these findings provide important information regarding mastery's relationship with fatigue and may inform interventions aiming to alleviate fatigue in caregivers.

3026 Dutch observational study on anaemia management with epoetin alfa in daily oncology practice – interim analysis results on 1000 patients

In April 2005 a phase III randomized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints: increase of lean body mass, decrease of resting energy expenditure (REE), increase of total daily physical activity, decrease of interleukin-6 and tumor necrosis factor-α, and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF).All patients were given as basic treatment polyphenols plus antioxidant agents α-lipoic acid, carbocysteine, and vitamins A, C, and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) l-carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus l-carnitine plus thalidomide. Treatment duration was 4 mo. The sample comprised 475 patients.By January 2007, 125 patients, well balanced for all clinical characteristics, were included. No severe side effects were observed. As for efficacy, an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3, 4, and 5, whereas arm 2 showed a significant worsening of lean body mass, REE, and MFSI-SF. Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1, 3, and 5 versus arm 2. A significant inferiority of arm 2 versus arms 3, 4, and 5 for the primary endpoints lean body mass, REE, and MFSI-SF was observed on the basis of t test for changes.The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen. The study is still in progress and the final results should confirm these data.

Fatigue in patients with ankylosing spondylitis: relationships with disease-specific variables, depression, and sleep disturbance

This study was designed to evaluate (a) the frequency of fatigue and its multi-dimensional nature, and (b) its association with demographic variables, disease-specific variables, and other variables, covering depression and sleep disturbance in patients with ankylosing spondylitis (AS). Sixty-two patients with AS were included in the study. Fatigue was assessed by the fatigue item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). While the disease activity was evaluated by the BASDAI, the functional state was assessed by Bath Ankylosing Spondylitis Functional Index, metrological measurements by Bath Ankylosing Spondylitis Metrology Index, global well-being by Bath Ankylosing Spondylitis Global Score, the pain on rest by VAS (0-10 cm), sleep disturbance by Pittsburgh Sleep Quality Index, and depressive symptoms by Zung Self-Rating Depression Scale. Fifty percent of the patients had severe fatigue. Multi-dimensional assessment with MFSI-SF enabled us to identify fatigue in more detail. The disease-specific variables, covering pain, stiffness, disease activity, and physical functioning, contributed significantly with both BASDAI fatigue and MFSI-SF as dependent variables, accounting for 61.3% and 44.7% of the variance, respectively. Disease activity was the most powerful predictor of both single-dimensioned and multi-dimensioned fatigue. It was also found that the contribution of depression on fatigue was 12%. In conclusion, it was observed that half of the patients had severe fatigue, and multi-dimensional assessment was provided to understand specific aspects of fatigue better. Even though disease activity had a considerable effect on fatigue, the effects of psychogenic factors, especially depression, should be taken into consideration in the management of AS.

Arousal frequency is associated with increased fatigue in obstructive sleep apnea.

ObjectiveFatigue is an important and often underemphasized symptom in patients with obstructive sleep apnea (OSA). Sleep fragmentation, i.e., arousals and disruptions in sleep architecture, is common in patients with OSA and may potentially contribute to their fatigue. We hypothesized that arousal frequency and changes in sleep architecture contribute to the fatigue experienced by patients with OSA.DesignSeventy-three patients with diagnosed but untreated OSA (AHI ≥ 15) were enrolled in this study. A baseline polysomnogram was obtained, and fatigue was measured with the Multidimensional Fatigue Symptom Inventory-short form (MFSI-sf). We evaluated the association between fatigue and arousals and various polysomongraphic variables, including sleep stages and sleep efficiency.ResultsSignificant correlations between MFSI-sf subscale scores and various arousal indices were noted. Emotional fatigue scores were associated with total arousal index (r = 0.416, p = .021), respiratory movement arousal index (r = 0.346, p = .025), and spontaneous movement arousal index (r = 0.378, p = .025). Physical fatigue scores were associated with total arousal index (r = 0.360, p = .033) and respiratory movement arousal index (r = 0.304, p = .040). Percent of stage 1 sleep and REM sleep were also associated with physical and emotional fatigue scores. Hierarchal linear regression analysis demonstrated that emotional fatigue scores were independently associated with spontaneous movement arousals after controlling for age, body mass index, depression, and sleep apnea severity.ConclusionsThese findings suggest that arousals may contribute to the fatigue seen in patients with OSA.

Association of fatigue and psychological distress with quality of life in patients with a previous venous thromboembolic event

Health-related quality of life (QoL) has been associated with several social and medical conditions in patients with deep vein thrombosis (DVT) and pulmonary embolism (PE). To the best of our knowledge, there is no study investigating the relationship of QoL with psychological variables in this patient population. We assumed as a hypothesis an association between heightened levels of fatigue and psychological distress, as well as decreased QoL in patients with an objectively diagnosed venous thromboembolic event. Study participants were 205 consecutively enrolled out-patients (47.4 years, 54.6% men) with DVT and/or PE. Approximately 10 days before blood collection for thrombophilia work-up, QoL, fatigue, and psychological distress were assessed using the Short Form Health Survey (SF-12), the Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) as well as the Hospitality Anxiety and Depression scale (HADS). After controlling for demographic and medical factors, fatigue (p < 0.01) but not psychological distress (p>0.05) was negatively associated with physical QoL, explaining 11.0% of the variance. Fatigue (p < 0.001) and psychological distress (p < 0.001) were significant predictors of mental QoL, explaining an additional 36.2% and 3.6% of the variance. Further analyses revealed that all subscales of the HADS (e.g. anxiety and depression) and of the MFSI-SF (e.g. general fatigue, physical fatigue, emotional fatigue, mental fatigue and vigor) were significant predictors of mental QoL. MFSI-SF subscales also predicted physical QoL. The findings suggest that fatigue and psychological distress substantially predict QoL in patients with a previous venous thromboembolic event above and beyond demographic factors.

Correlation between anemia, unintentional weight loss and inflammatory status on cancer-related fatigue and quality of life before chemo and radiotherapy

Summary Background Cancer-related anemia is considered a side effect of treatment and the most important cause of fatigue. The object of the current study was to investigate the possible correlation between anemia, unintentional weight loss and systemic inflammation on cancer-related fatigue and quality of life before chemo and radiotherapy. Patients and methods One hundred and sixty four consecutive outpatients affected by solid tumor of different origins were enrolled. In all patients, anemia, unintentional weight loss, C-reactive protein, fatigue (Multidimensional Fatigue Symptom Inventory-Short Form) and quality of life (EUROQOL EQ-5D) were assessed before treatment. Results Thirty two percent of the patients were anemic before treatment. Anemia was prevalent in case of unintentional weight loss (p = 0.001) and in recent surgery (p = 0.011), not in patients with high C-reactive protein (p = 0.181). Anemia was weight loss-related (p = 0.001). Forty seven percent of the patients suffering from unintentional weight loss before treatment. Weight loss was prevalent in case of C-reactive protein ≥10 mg/dL (p = 0.004), but not in case of recent surgery (p = 0.150). Weight loss was C-reactive protein-related (p = 0.001). In the multivariate analysis only anemia and weight loss influenced quality of life (p = 0.031), (p = 0.002) and fatigue (p = 0.016), (p = 0.036) independently. Conclusion Our data suggest that management of weight loss should deserve in cancer patients the same attention as the management of anemia, inflammatory status and pain.

Predictors of fatigue in obstructive sleep apnea

The objective of this study was to determine potential inflammatory predictors of fatigue in obstructive sleep apnea (OSA). Fifty-six women and men untreated OSA patients had their sleep monitored with polysomnography. Fatigue was assessed by the Multidimensional Fatigue Symptom Inventory-Short Form. Depressed mood was assessed by the Center for Epidemiologic Studies-Depression Scale. Blood was drawn to assess circulating levels of Interleukin-6 (IL-6) and soluble tumor necrosis factor receptor I (sTNF-RI). Age, gender, body mass index (BMI), blood pressure, OSA severity, depressed mood, and inflammatory biomarkers were entered into a hierarchical multiple linear regression analysis predicting self-reported fatigue. Approximately 42% of the patients reported significant amounts of fatigue. Higher BMI (p = 0.014), greater depressed mood (p = 0.004), and higher sTNF-RI levels (p = 0.033) were independent predictors of fatigue in the final model (full model R2 = .571; p = .003). Age, gender, blood pressure and apnea severity were unrelated to fatigue. The findings suggest that in addition to depressed mood, fatigue in OSA may be associated with increased body weight and elevated levels of the proinflammatory cytokine receptor sTNF-RI. The findings support a linkage between the widely reported fatigue in OSA and a sleep-related component of inflammation.

Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results

Objective In April 2005 a phase III randomized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints: increase of lean body mass, decrease of resting energy expenditure (REE), increase of total daily physical activity, decrease of interleukin-6 and tumor necrosis factor-α, and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF). Methods All patients were given as basic treatment polyphenols plus antioxidant agents α-lipoic acid, carbocysteine, and vitamins A, C, and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) l-carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus l-carnitine plus thalidomide. Treatment duration was 4 mo. The sample comprised 475 patients. Results By January 2007, 125 patients, well balanced for all clinical characteristics, were included. No severe side effects were observed. As for efficacy, an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3, 4, and 5, whereas arm 2 showed a significant worsening of lean body mass, REE, and MFSI-SF. Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1, 3, and 5 versus arm 2. A significant inferiority of arm 2 versus arms 3, 4, and 5 for the primary endpoints lean body mass, REE, and MFSI-SF was observed on the basis of t test for changes. Conclusion The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen. The study is still in progress and the final results should confirm these data.

Correspondence Between Daily and Weekly Fatigue Reports in Breast Cancer Survivors

Fatigue is a contributor to decreased quality of life and one of the most common symptoms reported by cancer survivors. Most assessment of fatigue has been retrospective and/or unidimensional. Single-item visual analogue scale ratings are commonly used, despite arguments that fatigue is better conceptualized as multidimensional. The relationships of daily to weekly ratings of fatigue, or of unidimensional to multidimensional assessments, have not been explored. Twenty-five breast cancer survivors provided daily ratings of fatigue and completed the Multidimensional Fatigue Symptom Inventory-Short Form weekly for one month. Using hierarchical linear modeling, stronger relationships of weekly ratings to average and peak rather than most recent daily ratings were found. Visual analogue scale ratings shared more variance with the General Fatigue subscale than with the other four fatigue dimensions measured. Findings suggest that different information is captured by daily versus weekly reports, and that although visual analogue scale ratings can provide a quick assessment of general fatigue, they do not capture other important dimensions.

A Phase II Study with Antioxidants, Both in the Diet and Supplemented, Pharmaconutritional Support, Progestagen, and Anti-Cyclooxygenase-2 Showing Efficacy and Safety in Patients with Cancer-Related Anorexia/Cachexia and Oxidative Stress

To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress. An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF). From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the treatment was effective and more importantly was shown to be safe. The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study is warranted.

Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy

Objective Fatigue is a multidimensional symptom that is described in terms of perceived energy, mental capacity, and psychological status: it can impair daily functioning and lead to negative effects on quality of life. It is one of the most common side effects of chemotherapy and radiotherapy. In recent studies, l-carnitine (LC) supplementation has been demonstrated to be able to improve fatigue symptoms in patients with cancer. Methods In the present study we tested the efficacy and safety of LC supplementation in a population of patients who had advanced cancer and developed fatigue, high blood levels of reactive oxygen species, or both. As outcome measures we evaluated fatigue and quality of life in relation to oxidative stress, nutritional status, and laboratory variables, mainly levels of reactive oxygen species, glutathione peroxidase, and proinflammatory cytokines. From March to July 2004, 12 patients who had advanced tumors (50% at stage IV) at different sites were enrolled (male-to-female ratio 2:10, mean age 60 y, range 42–73). Patients were only slightly anemic (hemoglobin 10.9 g/dL) and hemoglobin levels did not change after treatment. LC was administered orally at 6 g/d for 4 wk. All patients underwent antineoplastic treatment during LC supplementation. Results Fatigue, as measured by the Multidimensional Fatigue Symptom Inventory—Short Form, decreased significantly, particularly for the General and Physical scales, and for quality of life in each subscale of quality of life in relation to oxidative stress. Nutritional variables (lean body mass and appetite) increased significantly after LC supplementation. Levels of reactive oxygen species decreased and glutathione peroxidase increased but not significantly. Proinflammatory cytokines did not change significantly. Conclusion Improvement of symptoms with respect to fatigue and quality of life in relation to oxidative stress may be explained mainly by an increase in lean body mass, which may be considered the most important nutritional or functional parameter in assessing the cachectic state of patients. In this view, fatigue with related symptoms can well be considered an important constituent of cancer-related anorexia cachexia syndrome.

Fatigue in gynaecological cancer patients: a pilot study

Fatigue is a frequent complaint of women with cancer. However, the incidence of fatigue has not been well studied, in particular gynaecological cancer, which despite its prevalence has received minimal investigation. The study aims were (1) to explore the symptoms experienced in a gynaecological cancer population, primarily fatigue and (2) to determine the acceptability of a fatigue questionnaire for use in a longitudinal survey. Over the course of 1 month, women with gynaecological cancer attending a Regional Cancer Centre completed a demographic and symptom questionnaire and the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Of the 32 individuals approached, 30 agreed to participate (mean age, 61 years; the most common treatment received was surgery followed by chemotherapy n=11; mean time from commencement of treatment, including surgery = 3 months). All participants completed the MFSI-SF. Tiredness was the most commonly reported symptom, experienced by 90% of subjects and the most frequently stated worst symptom, reported by 23.3%. Furthermore, 23 of 27 subjects reported that tiredness interfered completely with their daily living. The MFSI-SF mean total fatigue score was 14.4 (SD 15.9), ranging from -15 to 50. The possible total fatigue score ranges from -24 to 96. Despite the heterogeneous nature of the group, all participants completed the MFSI-SF. The study suggests that fatigue could be a problem for this population group. Thus, a longitudinal survey using the MFSI-SF to investigate the phenomenon further would appear feasible and justified.