Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients

Ifosfamide and cisplatin cause urinary loss of carnitine, which is a fundamental molecule for energy production in mammalian cells. We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients. Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry. Patients were excluded if they had anaemia or other conditions thought to be causing asthenia. Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire. Treatment consisted of oral levocarnitine 4 g daily, for 7 days. Fifty patients were enrolled; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients. In the whole group, baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 (+/-6.4; standard deviation) and the mean plasma carnitine value was 20.9 microM (+/-6.8; standard deviation). After 1 week, fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 (+/-5.4; standard deviation) (P<.001). All patients achieved normal plasma carnitine levels. Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy. In selected patients, levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue. This compound deserves further investigations in a randomised, placebo-controlled study.     

癌症患者化疗前后疲劳状况及其影响因素

目的：调查肿瘤患者化疗前后疲劳状况并探讨其影响因素。方法：应用翻译的FSI量表及自行编制的疾病及一般情况登记表,对121例住院肿瘤患者进行面对面问卷式调查,计算FSI量表各维度得分,采用方差分析方法分析其主要影响因素。结果：肿瘤病人化疗前不同性别、不同肿瘤分期疲劳评分有明显差异（P〈0.05）。化疗后疲劳评分多有不同程度的增加,差异有统计学意义（P〈0.01）。使用不同化疗方案的患者化疗后疲劳评分有显著差异（P〈0.05）。化疗过程中有恶心呕吐症状者化疗后疲劳各维度评分均明显增高（P〈0.05）。结论：肿瘤病人化疗后疲劳评分明显增高。女性、肿瘤分期晚、联合化疗、化疗中有恶心呕吐症状疲劳评分较高,不同的化疗药物所导致的疲劳程度不同。     

癌症患者化疗前后疲劳状况及其影响因素

目的:调查肿瘤患者化疗前后疲劳状况并探讨其影响因素。方法:应用翻译的FSI量表及自行编制的疾病及一般情况登记表,对121例住院肿瘤患者进行面对面问卷式调查,计算FSI量表各维度得分,采用方差分析方法分析其主要影响因素。结果:肿瘤病人化疗前不同性别、不同肿瘤分期疲劳评分有明显差异(P<0.05)。化疗后疲劳评分多有不同程度的增加,差异有统计学意义(P<0.01)。使用不同化疗方案的患者化疗后疲劳评分有显著差异(P<0.05)。化疗过程中有恶心呕吐症状者化疗后疲劳各维度评分均明显增高(P<0.05)。结论:肿瘤病人化疗后疲劳评分明显增高。女性、肿瘤分期晚、联合化疗、化疗中有恶心呕吐症状疲劳评分较高,不同的化疗药物所导致的疲劳程度不同。     

Prevalence and course of fatigue in breast cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The purpose of this study was to determine the prevalence of fatigue and the course of fatigue as a function of chemotherapy in breast cancer patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective cohort study, a sample of 157 patients with breast cancer were interviewed, using the Rotterdam Symptom Checklist and the Multidimensional Fatigue Inventory, at the first, third and fifth cycle of adjuvant chemotherapy, as well as 4 and 12 weeks after the last cycle of adjuvant chemotherapy. Patients were treated with either a doxorubicin-containing schedule, or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). RESULTS: The courses of general and physical fatigue are to a large extent similar. After the last cycle of chemotherapy, the CMF group reported a significant increase in fatigue, which was followed by a significant reduction. In the doxorubicin group a significant increase in fatigue was only seen during the first cycles of chemotherapy. The fatigue experienced at the first and the last measurements do not differ significantly. CONCLUSIONS: The prevalence of fatigue increased significantly after the start of chemotherapy. After chemotherapy treatment the prevalence rate seemed to decline. A different impact of chemotherapy on the course of fatigue was found. In the doxorubicin group a direct increase in fatigue was found. In the CMF group a moderate direct increase occurred, followed by a delayed strong increase. An increase in fatigue was associated with a decrease in daily functioning. At all measurement occasions fatigue was affected by type of operation, such that women with a mastectomy were more fatigued than women that underwent a lumpectomy. Receiving radiotherapy also led to an increase in fatigue. With this knowledge breast cancer patients can be better informed about what they can expect. Further research should include interventions addressing how to reduce or cope with fatigue during as well as after receiving adjuvant chemotherapy.     

中药热熨敷技术对乳腺癌化疗患者癌因性疲乏的干预效果

目的:探讨中药热熨敷技术对乳腺癌化疗患者癌因性疲乏的干预效果。方法:将64例存在癌因性疲乏症状的乳腺癌化疗患者作为研究对象,采用随机数字法分为两组,对照组32例接受医院常规护理,实验组32例在接受医院常规护理的基础上,接受5天中药热熨敷技术干预。使用修订的Piper疲乏量表(RPFS)评价干预效果。结果:干预结束后, 实验组RPFS得分明显低于对照组(P<0.05)。与干预前比较,实验组RPFS得分较5天前无显著变化(P>0.05),而对照组RPFS得分较5天前明显升高(P<0.01)。结论:中药热熨敷可延缓随化疗进行而导致的癌因性疲乏的加重。     

Correlation between physical performance and fatigue in cancer patients

Background: Fatigue and a reduction in physical ability are common andoften severe problems of cancer patients regardless of disease stage andmodality of treatment. However, while physical performance can be assessedobjectively with laboratory tests, fatigue is a subjective phenomenon whoseperception is influenced by past experience and expectations for the future.Patients and methods: To evaluate the correlation between fatigue andphysical impairment, we assessed maximal physical performance with atreadmill test, and mental state with two questionnaires, the Profile ofMood States (POMS) and the Symptom Check List (SCL-90-R), in a successiveseries of 78 cancer patients with solid tumors or hematologicalmalignancies.Results: A weak association between fatigue and maximal physicalperformance was found (r = –0.30; P < 0.01). However, intensity offatigue showed a strong correlation with several indicators of psychologicaldistress such as depression (r = 0.68), somatization (r = 0.64) and anxiety(r = 0.63; P for all <0.001). Furthermore, patients with lower levels ofphysical performance had significantly higher scores for depression (P =0.005), somatization (P = 0.03) and anxiety (P = 0.08), and significantlylower scores for vigor (P = 0.05) than their counterparts whose physicalperformance was higher.Conclusions: We conclude that fatigue in cancer patients may be related tomood disturbance but appears to be independent of physical performance.Moreover, low physical performance can be viewed as an independent predictorof mental distress in cancer patients.     

Long-term fatigue state in postoperative patients with breast cancer简

Objective：To investigate the prevalence of long-term fatigue,anxiety,depression and social support,and the relationships among these symptoms in postoperative patients with breast cancer.Methods：A total of 180 postoperative patients with breast cancer meeting criterion were recruited in this cross-sectional study.The Brief Fatigue Inventory （BFI）,Hospital Anxiety and Depression Scale （HADS） and The Social Support Survey-Chinese version were used to assessing the fatigue,anxiety and depression,Social support of participants.The magnitude of the relationship among the symptoms of fatigue and other variables was measured by Spearman Rho correlation.Results：The prevalence of long-term fatigue was 52.7％,and 18.3％ occurred moderate/severe fatigue.Two-thirds of patients had a basal social support,only 12.8％ of patients had better-perceived social support.Results of HADS showed that 16.7％ and 21.1 ％ of the participants have anxiety or depression disorder.Moderate/severe fatigue was negatively correlated with social support （r=-0.158,P=0.038） and positively correlated with age （r=0.132,P=0.042）,chemotherapy （r=0.297,P=0.027）,anxiety （r=0.324,P=0.018） and depression （r=0.211,P=0.034）.Conclusions：Long-term fatigue was highly prevalent among over half of postoperative patients with breast cancer,and moderate/severe fatigue was associated with social and psychological factors such as social support,anxiety and depression.Our results suggest that overall nursing care may be a more effective manner in improving fatigue and quality of life.     

(Pre)treatment risk factors for late fatigue and fatigue trajectories following radiotherapy for breast cancer

Fatigue is common in breast-cancer survivors. Our study assessed fatigue longitudinally in breast cancer patients receiving adjuvant radiotherapy (RT) and aimed to identify risk factors associated with long-term fatigue and underlying fatigue trajectories. Fatigue was measured in a prospective multicenter cohort (REQUITE) using the Multidimensional Fatigue Inventory (MFI-20) and analyzed using mixed models. Multivariable logistic models identified factors associated with fatigue dimensions at 2 years post-RT and latent class growth analysis identified individual fatigue trajectories. A total of 1443, 1302, 1203 and 1098 patients completed the MFI-20 at baseline, end of RT, after 1 and 2 years. Overall, levels of fatigue significantly increased from baseline to end of RT for all fatigue dimensions (P < .05) and returned to baseline levels after 2 years. A quarter of patients were assigned to latent trajectory high (23.7%) and moderate (24.8%) fatigue classes, while 46.3% and 5.2% to the low and decreasing fatigue classes, respectively. Factors associated with multiple fatigue dimensions at 2 years include age, BMI, global health status, insomnia, pain, dyspnea and depression. Fatigue present at baseline was consistently associated with all five MFI-20 fatigue dimensions (OR_{GeneralFatigue} = 3.81, P < .001). From latent trajectory analysis, patients with a combination of factors such as pain, insomnia, depression, younger age and endocrine therapy had a particularly high risk of developing early and persistent high fatigue years after treatment. Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered.     

Course of mental fatigue and motivation in breast cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The purpose of this study is to determine the course of fatigue referring to cognitive symptoms (scale 'mental fatigue') as well as the motivation to start any activity (scale 'reduced motivation'), as a function of chemotherapy, in breast cancer patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective cohort study a sample of 157 patients with breast cancer was interviewed at the first, third and fifth cycle of adjuvant chemotherapy as well as 4 and 12 weeks after completion of adjuvant chemotherapy. Patients were treated with standard adjuvant chemotherapy, either a doxorubicin containing schedule or CMF (cyclophosphamide, methotrexate and fluorouracil). The psychological dimensions of fatigue were measured by the Multidimensional Fatigue Inventory. A linear multilevel model was used for analysing the courses. RESULTS: The course of mental fatigue and motivation were not affected by the type of chemotherapy. The course of mental fatigue and motivation varied, but seemed to be stable during the treatment of chemotherapy. After the completion of chemotherapy, a weak improvement was seen. Relatively many patients experienced depressive symptoms during the study. These symptoms were correlated with both dimensions of fatigue. At all measurements mental fatigue was influenced by type of operation where women with a mastectomy were significantly more mentally fatigued than women that had undergone a lumpectomy, but nevertheless they were significantly more motivated to start any activity. Age, marital status, number of treatments and the interval between the operation and the first treatment of chemotherapy also seemed to be important determinants. CONCLUSIONS: An unequivocal pattern of mental fatigue and reduced motivation during as well as after adjuvant chemotherapy was not found. Depressive symptoms were definitely related to these variables. Type of operation had a significant impact on mental fatigue and motivation to start any activity. Health care providers should be aware of the high rate of patients who experience depressive symptoms during and after the treatment of chemotherapy. Further research should include the trajectory preceding adjuvant chemotherapy and a longer study period afterwards. Moreover, the exact influence of the variables 'age', 'marital status', 'number of treatments' and 'the interval between the operation and the first treatment of chemotherapy' on fatigue is unclear and needs further study.     

运动干预对卵巢癌化疗患者负性情绪、癌因性疲乏和生活质量的影响

目的探讨运动干预对卵巢癌化疗患者负性情绪、癌因性疲乏和生活质量的影响。方法选取200例卵巢癌化疗患者,依据干预方式的不同分为对照组和观察组,每组100例。对照组患者接受常规干预措施,观察组患者在此基础上联合运动干预。干预前和干预3个月后,采用焦虑自评量表(SAS)、抑郁自评量表(SDS)比较两组患者的负性情绪,采用Piper疲乏修正量表(RPFS)评估两组患者的癌因性疲乏程度,采用世界卫生组织生活质量量表(WHOQOL-100)评估两组患者的生活质量。结果干预前,两组患者SAS、SDS、RPFS和WHOQOL-100各维度评分比较,差异均无统计学意义(P﹥0.05)。干预3个月后,两组患者SAS、SDS、RPFS各维度评分均低于本组干预前,WHOQOL-100各维度评分均高于本组干预前,且观察组SAS、SDS、RPFS各维度评分均低于对照组患者,WHOQOL-100各维度评分均高于对照组患者,差异均有统计学意义(P﹤0.05)。结论运动干预能够有效缓解卵巢癌化疗患者焦虑抑郁情绪,减轻癌因性疲乏程度,从而提高患者生活质量。     

Determinants of chronic fatigue in disease-free breast cancer patients: a cross-sectional study.

BACKGROUND: Quality of life after cancer treatment becomes more important as the number of long-term survivors increases. This study aimed to investigate complaints of fatigue after treatment for breast cancer. PATIENTS AND METHODS: The study patients were 150 women who had finished curative treatment for breast cancer by a mean of 29 months before commencement of this study. Measurements included computerised questionnaires and a daily Self-Observation List. RESULTS: Thirty-eight per cent of the sample were severely fatigued, compared with 11% in a matched sample of women without a history of cancer. No association was found between fatigue and former treatment. The 'severely fatigued disease-free breast cancer patient' scored more 'problematic' on psychological well-being, functional impairment, sleep disturbance, physical activity, social support, neuropsychological and social functioning compared with the 'non-severely fatigued disease-free breast cancer patient'. Furthermore, the severely fatigued patients had a lower sense of control with respect to their fatigue complaints and stronger breast cancer- and psychologically-related attributions with regard to the causes of fatigue compared with the non-severely fatigued patients. Regression analyses indicated that sleep disturbance, physical activity and causal attributions contributed significantly to the subjective experience of fatigue. CONCLUSIONS: Severe fatigue is a problem for almost 40% of the sample of breast cancer survivors. Severe fatigue is related to physical, psychological, social, cognitive and behavioural factors.     

化疗患者的癌性疲劳干预研究进展

癌症的发病率正在逐年上升,但随着肿瘤治疗方法的不断发展和医学模式的转变,癌症患者的生存期得到了显著延长,同时提高患者的生活质量也日益受到关注。癌性疲劳被认为是癌症患者最严重的并发症,严重影响着患者的生活质量。尽管癌性疲劳的发生率很高,但其病理生理学机制尚不明确,临床上尚无理想的干预措施,患者的疲劳尚未得到足够重视和及时治疗。本文对化疗患者癌性疲劳的相关干预研究进行综述,以期指导临床应用。     

A qualitative study to explore the experience of fatigue in cancer patients

Fatigue – which is a complex, multicausal, and multidimensional subjective experience – is today the most frequently reported symptom from patients with cancer. The aim of this study was to explore the experience of fatigue in cancer patients and to describe the categories and dimensions of the symptoms. A qualitative method – grounded theory – was used. Unstructured, tape-recorded interviews with 15 cancer patients were used for data collection. The categories found in this study illustrate fatigue as a process. Three major categories were found: (1) experiences (of loss, need, malaise, psychological stress, emotional affection, abnormal weakness, difficulties in taking the initiative); (2) consequences (social limitation, affected self-esteem, affected quality of life); and (3) actions (coping). The categories were constructed on the basis of dimensions with subordinated qualities. Knowledge concerning the different expressions of fatigue is important in caring for patients with cancer. The results from this study may contribute to a better understanding of how a cancer patient can experience and express fatigue and how the symptoms may affect the patient.     

Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial

Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group‐based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group‐based interventions. One‐hundred‐one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group‐based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20‐item multidimensional questionnaire, QoL with the EORTC QLQ‐C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between‐group p = 0.098 and 0.052 overall, and p = 0.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p‐interaction = 0.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group‐based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy.     

The relationship between fatigue and sleep in cancer patients: a review

Fatigue is a major complaint among cancer patients, yet it is unknown whether cancer-related fatigue experienced during the day relates to sleep/wake cycles or to the quality and quantity of sleep obtained at night. Although it is not well defined or well understood at present, cancer-related fatigue is generally regarded as a form of tiredness that does not improve following rest or sleep. Objectively recorded sleep and biological rhythms have not been well investigated in these patients, but it appears that most cancer patients may in fact not be getting a good night's sleep. Evidence is accumulating that sleep is often disturbed in cancer patients, probably owing to a variety of causes. We posit that some degree of cancer-related fatigue experienced during the day may relate to sleep/wake cycles or to the quality and quantity of sleep obtained at night. Different components or dimensions of fatigue (physical, attentional/cognitive, emotional/affective, etc.) are probably associated in some way with disrupted sleep and desynchronized sleep/wake rhythms. These associations may change in measurable ways prior to treatment, during treatment and after treatment completion. In cancer patients, as in other medically ill patients, sleep that is inadequate or unrefreshing may be important not only to the expression of fatigue, but to the patients' quality of life and their tolerance to treatment, and may influence the development of mood disorders and clinical depression. This review summarizes the state of the literature on fatigue, sleep and circadian rhythms.     

The impact of hemoglobin levels on fatigue and quality of life in cancer patients.

BACKGROUND: Although fatigue is a commonly reported symptom in cancer patients its etiology is still poorly understood. The objective of the present study was to investigate the relationship between hemoglobin (Hb) levels and the subjective experience of fatigue and quality of life in cancer patients with mild or no anemia undergoing chemotherapy. PATIENTS AND METHODS: Sixty-eight cancer patients (25 colorectal, 26 lung and 17 ovarian cancer) presently undergoing chemotherapy participated in the study. Fatigue was measured with the Multidimesional Fatigue Inventory (MFI-20), quality of life with The European Organization for Research and Treatment of Cancer QLQ-C30. In order to provide normative data for fatigue levels, the MFI-20 was also completed by a sex- and age-matched sample of 120 healthy controls. RESULTS: Compared with healthy subjects, cancer patients experienced significantly higher levels of subjective fatigue. Correlations between Hb values and subscales of the MFI-20 were moderate with a tendency to increase during chemotherapy. Hb values alone, however, do not fully account for the observed fatigue. Other symptoms, especially pain, dyspnea and sleep disturbances, also showed an association with perceived fatigue. CONCLUSIONS: Despite significant correlations, these results indicate that Hb values only partially explain subjectively experienced fatigue and quality of life in cancer patients. It is suggested therefore that the treatment of fatigue must be multidimensional and involve all areas which contribute to the syndrome.