Cancer Treatment-related Fatigue Research Articles

Impact of Vitamin B12 on outcome of Early Stage Luminal A and B Breast Cancer, single center experience

Abstract Background: Despite the fact that many studies have shown that vitamin B12 has no benefit in chemotherapy-induced peripheral neuropathy, many doctors describe vitamin B12 for chemotherapy or hormonal treatment. Some studies have shown that it is effective in cancer treatment-related fatigue, especially with B12 deficiency anaemia. Vitamin B12 has anti-oxidant properties through a variety of mechanisms. Many clinical recommendations are against using antioxidants during cancer treatment; there is concern that using dietary supplements, particularly antioxidants, during treatment may reduce treatment efficacy. Methods: This is a retrospective study as part of Zeinab Gaber's thesis that reviewed the electronic records of 129 female breast cancer patients with stage I and II luminal (A&B) who were treated at the clinical oncology department, faculty of medicine, Beni-Suef University, Egypt, from the beginning of January 2015 to the end of December 2019. Results: There was no disease-free survival (DFS) difference in luminal A breast cancer that received or did not receive vitamin B12, with median DFS 80 months versus 81 months for received and not received Vitamin B12, respectively (SE 2.55-3.54, 95% CI, 0.74 to 0.88; P 0.843), and there was no DFS difference in luminal B breast cancer that received or did not receive Vitamin B12, with median DFS 76 months versus 73 months for received and not received Vitamin. There was no overall survival (OS) difference in luminal A breast cancer that received or did not receive vitamin B12, with median OS 83 months versus 82 months for received and not received Vitamin B12, respectively (SE 2.16-2.73, 95% CI, 0.78 to 0.89; P 0.865), and there was no OS difference in luminal B breast cancer that received or did not receive Vitamin B12, with median OS 81 months versus 80 months for received and not received Vitamin B12, respectively (SE 1.78-2.68, 95% CI, 0.75 to 0.85; P 0.572). Conclusion: Vitamin B12 had no effect on DFS or OS in luminal A or B early breast cancer patients and can be used safely when indicated.

An 8-week exercise study to improve cancer treatment related fatigue and QOL among African American breast cancer patients undergoing radiation treatment: A pilot randomized clinical trial

Cancer treatment related fatigue (CTRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors. The primary objective of the PEDLAR study is to test the feasibility of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CTRF and improving health-related QOL among African-American breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in African-American women with breast cancer. It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group. Participants in intervention group reported high satisfaction with exercise and adherence was >75% for exercise sessions. African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).

Oncological Treatment-Related Fatigue in Oncogeriatrics: A Scoping Review.

Simple SummaryFatigue in older patients has multiple etiologies, as this symptom may be cancer-related, treatment-related, age-related, or part of frailty syndrome. Physicians need to identify this symptom and understand its risk factors but also evaluate the risk/benefit ratio of cancer treatments considering the risk of impairing the patient’s quality of life. This scoping review was aimed to present the level of information currently available on any-grade fatigue and grade 3 or more fatigue for each cancer treatment regimen, either in general or in older populations, for the most prevalent tumors.Fatigue is a highly prevalent symptom in both cancer patients and the older population, and it contributes to quality-of-life impairment. Cancer treatment-related fatigue should thus be included in the risk/benefit assessment when introducing any treatment, but tools are lacking to a priori estimate such risk. This scoping review was designed to report the current evidence regarding the frequency of fatigue for the different treatment regimens proposed for the main cancer indications, with a specific focus on age-specific data, for the following tumors: breast, ovary, prostate, urothelium, colon, lung and lymphoma. Fatigue was most frequently reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) versions 3 to 5. A total of 324 regimens were analyzed; data on fatigue were available for 217 (67%) of them, and data specific to older patients were available for 35 (11%) of them; recent pivotal trials have generally reported more fatigue grades than older studies, illustrating increasing concern over time. This scoping review presents an easy-to-understand summary that is expected to provide helpful information for shared decisions with patients regarding the anticipation and prevention of fatigue during each cancer treatment.

Association of Fatigue, Quality of Life and Functional Capacity in Breast Cancer Patients Receiving Adjuvant Chemotherapy

Objectives: Cancer treatment related fatigue is a common and distressing symptom among breast cancer patients. With a greater longevity promote by advances in therapeutics & early diagnosis, interest has shifted to the assessment of quality of life (QOL). The concept of functional capacity has been used extensively in disability and rehabilitation research as an indicator of an individual’s ability to engage in physical activity. The aim of this study was to find the association of fatigue, QOL and functional capacity in post-operative breast cancer patients receiving adjuvant therapy.Materials and Methods: A total 30 participants who were receiving third cycle of chemotherapy were recruited from the Cancer Hospital. Facet fatigue questionnaire, FACT B questionnaire and 6-minute walk test (6MWT) were used for the assessment purpose of fatigue, QOL and functional capacity, respectively. Results: The Spearman’s correlation confirmed that the fatigue is strongly associated with subscale score of Fact B and very strongly associated with total score of fact B, Fact G and TOI. There was moderate association between the fatigue and functional capacity. There were above average values in total and subscale scores of QOL but among all the subscale scores of QOL, breast cancer subscale score was having lower value compared to others and social well being score was higher. Conclusion: Fatigue is having strong association with quality of life and moderate effect with functional capacity in these patients. Specific breast cancer related health is having more association among other quality of life aspects and social well being is least affected.
 

Effects of high-intensity interval training compared with resistance training in prostate cancer patients undergoing radiotherapy: a randomized controlled trial.

Exercise training has shown beneficial effects in the management of radiotherapy-related side effects in prostate cancer (PCa) patients undergoing radiation therapy (RT). However, the optimal modality of the exercise programs have not been yet determined. The aim of this randomized controlled trial was to investigate the effects of high-intensity interval training (HIIT) and resistance training (RES) compared to usual care (UC) on cancer-treatment-related fatigue (CTRF) (primary outcome), quality of life, depression, daytime sleepiness, insomnia, sleep quality, functional exercise capacity and executive function in PCa patients during RT. PCa patients undergoing RT with or without ADT were randomized in HIIT, RES or UC. Both exercise programs included three sessions per week during 5-8 weeks. HIIT consisted of 8-15 × 60 s intervals (≥85% maximal heart rate). RES was performed with 1-3 sets of 8-12 repetitions for each large muscle groups. The primary outcome was changed in CTRF measured with the Functional Assessment of Chronic Illness Therapy-Fatigue. Seventy-two subjects (69.1 ± 8.2 years) completed the study. No exercise-related adverse events occurred. HIIT (p = 0.012) and RES (p = 0.039) training attenuated increases in CTRF compared to UC. Functional exercise capacity, evaluated by the 6-min walk test, increased after HIIT (p = 0 = 0.43) and RES (p = 0.041) compared to UC (+0.1%). No other secondary variables were different between groups. Both intervention groups displayed beneficial effects on CTRF and functional exercise capacity in PCa patients undergoing RT. In addition, HIIT and RES are both safe with an excellent attendance rate to the exercise sessions.

I-Move, a personalised exercise intervention for patients with advanced melanoma receiving immunotherapy: a randomised feasibility trial protocol

IntroductionThere is increasing evidence demonstrating the benefits of exercise in counteracting cancer treatment-related fatigue. Immunotherapy is an established treatment for advanced melanoma, and is associated with fatigue in a third...

Onkologische Rehabilitation integriert in die Behandlungspfade der modernen Onkologie

Cancer Rehabilitation: integrated in the care pathways of modern oncology Abstract. People suffering from cancer are affected both by the cancer disease and from side-effects of multimodal anticancer interventions such as surgical, radiooncological and drug therapies. These effects can lead to physical, emotional, social, intellectual or existential functional deficits, which presence and impact are often underrecgonized by oncology professionals. Oncological rehabilitation targets such deficits by multimodal, transprofessionally delivered, goal steered and human centered coordinated interventions. Indications for oncological rehabilitation exist in situations before, during, between and after cancer therapies in both curative and non-curative intention. This includes for example prehabilitation, rehabilitation of myeloma patients between transplantions, of patients suffering from cancer-treatment related fatigue or from advanced cancer undergoing anticancer treatment: basically, every patient in modern oncology who suffers from substantial functional deficits. Oncological rehabilitation defines concrete goals in order to achieve the functions in comparison to before the deficits occurred, the overlaying aims to achieve an optimal self-determination and independence. A profound understanding of the oncological situation by both the patient and professionals is necessary to define realistic goals. Based on - and steered by - these goals, oncological rehabilitation employs specific rehabilitation interventions, supported by a transprofessionally coordinated team of exercise specialists, physiotherapy, ergotherapy, speech, art and music therapists, nutritional, socialwork and psycho-oncological counsellors, as well as activating and therapy-accompanying nurses and physicians. Competence in both cancer disease and anticancer treatment side effects as well as rehabilitation procedures is relevant in goal setting and rehabilitative treatment guidance as well as administration of systemic cancer therapies during oncological rehabilitation. It is a reality in modern oncology that many cancer patients require both oncological rehabilitation and ongoing anticancer treatments. The integration of oncological rehabilitation in the treatment pathways of modern oncology demands new models - including new forms of reimbursement - making allowance for the realities and needs of modern oncology.

Psychometric Properties of a Developed Arabic Instrument to measure Cancer Treatment-Related Fatigue in Saudi Children

Psychometric Properties of a Developed Arabic Instrument to measure Cancer Treatment-Related Fatigue in Saudi Children

Altered Cd8+ T lymphocyte Response Triggered by Arginase 1: Implication for Fatigue Intensification during Localized Radiation Therapy in Prostate Cancer Patients.

Fatigue, the most common side effect of cancer treatments, is observed to intensify during external-beam radiation therapy (EBRT). The underlying molecular mechanisms remain unclear. This study investigated the differentially expressed genes/proteins and their association with fatigue intensification during EBRT. Fatigue scores measured by FACT-F and peripheral blood were collected prior to treatment (baseline D0), at midpoint (days 19-21, D21) and endpoint (days 38-42, D42) from men (n=30) with non-metastatic prostate cancer undergoing EBRT. RNA extracted from peripheral blood was used for gene expression analysis. Plasma arginase I and arginine were examined using ELISA and liquid chromatography-tandem mass spectrometry. Differences in fatigue scores, gene and protein expression between times points following EBRT were analyzed by one way ANOVA followed by Post Hoc t-test. Fatigue scores decreased significantly from baseline (44.6 ± 8.1) to midpoint (37.3 ± 10.6, p=0.000, low scores indicating high fatigue) and to endpoint (37.4 ± 10.1, p=0.001) during EBRT. ARG1 (encoding arginase type 1) was significantly up regulated from baseline to midpoint of EBRT (fold change =2.41, p<0.05) whereas genes associated with the adaptive immune functional pathway (CD28, CD27, CCR7, CD3D, CD8A and HLA-DOB) were significantly downregulated >2-fold between the study time points. The changes in gene expression were associated with patient reported fatigue intensity. Moreover, the upregulation of ARG1 was negatively correlated with the absolute lymphocyte count (R2=0.561, p=0.01) only in the high level of fatigue group (n=17) during EBRT. Increased ARG1 expression is known to result in arginine deficiency, which leads to immunosuppression by impairing lymphocyte proliferation and activation. EBRT-induced ARG1 upregulation may play an essential role in fatigue intensification via the arginine deficiency and suppression of T-cell proliferation pathways. These findings may provide novel insights into the molecular-genetic mechanisms underlying the development and intensification of cancer treatment-related fatigue.

The Etiology and management of radiotherapy-induced fatigue.

Fatigue is one of the most common side-effects accompanying radiotherapy, but arguably the least understood. Radiotherapy-induced fatigue (RIF) is a clinical subtype of cancer treatment-related fatigue. It is described as a pervasive, subjective sense of tiredness persisting over time, interferes with activities of daily living, and is not relieved by adequate rest or sleep. RIF is one of the early side-effects and long-lasting for cancer patients treated with localized radiation. Although the underlying mechanisms of fatigue have been studied in several disease conditions, the etiology, mechanisms, and risk factors of RIF remain elusive, and this symptom remains poorly managed. The purpose of this paper is to review and discuss recent articles that defined, proposed biologic underpinnings and mechanisms to explain the pathobiology of RIF, as well as articles that proposed interventions to manage RIF. Understanding the mechanisms of RIF can describe promising pathways to identify at-risk individuals and identify potential therapeutic targets to alleviate and prevent RIF using a multimodal, multidisciplinary approach.

Electroencephalogram power changes as a correlate of chemotherapy-associated fatigue and cognitive dysfunction

Persistent fatigue and cognitive dysfunction are poorly understood potential long-term effects of adjuvant chemotherapy. In this pilot study, we assessed the value of electroencephalogram (EEG) power measurements as a means to evaluate physical and mental fatigue associated with chemotherapy. Women planning to undergo adjuvant chemotherapy for breast cancer and healthy controls underwent neurophysiologic assessments at baseline, during the time of chemotherapy treatment, and at 1 year. Repeated measures analysis of variance was used to analyze the data. Compared with controls, patients reported more subjective fatigue at baseline that increased during chemotherapy and did not entirely resolve by 1 year. Performance on endurance testing was similar in patients versus controls at all time points; however, values of EEG power increased after a physical task in patients during chemotherapy but not controls. Compared with controls, subjective mental fatigue was similar for patients at baseline and 1 year but worsened during chemotherapy. Patients performed similarly to controls on formal cognitive testing at all time points, but EEG activity after the cognitive task was increased in patients only during chemotherapy. EEG power measurement has the potential to provide a sensitive neurophysiologic correlate of cancer treatment-related fatigue and cognitive dysfunction.

Small molecule kinase inhibitors block the ZAK-dependent inflammatory effects of doxorubicin

The adverse side effects of doxorubicin, including cardiotoxicity and cancer treatment-related fatigue, have been associated with inflammatory cytokines, many of which are regulated by mitogen-activated protein kinases (MAPKs). ZAK is an upstream kinase of the MAPK cascade. Using mouse primary macrophages cultured from ZAK-deficient mice, we demonstrated that ZAK is required for the activation of JNK and p38 MAPK by doxorubicin. Nilotinib, ponatinib and sorafenib strongly suppressed doxorubicin-mediated phosphorylation of JNK and p38 MAPK. In addition, these small molecule kinase inhibitors blocked the expression of IL-1β, IL-6 and CXCL1 RNA and the production of these proteins. Co-administration of nilotinib and doxorubicin to mice decreased the expression of IL-1β RNA in the liver and suppressed the level of IL-6 protein in the serum compared with mice that were injected with doxorubicin alone. Therefore, by reducing the production of inflammatory mediators, the inhibitors identified in the current study may be useful in minimizing the side effects of doxorubicin and potentially other chemotherapeutic drugs.

TNF-α deficiency as protection against sickness behavior related to external beam radiation of the pelvis in mice.

208 Background: Prostate cancer patients undergoing localized external beam radiation therapy (EBRT), experience significant fatigue during treatment, which can affect physical functioning and QOL. We hypothesize that cancer treatment related fatigue (CTRF) is the same as sickness behavior caused, in part, by increases in TNF-α. Our previous data demonstrate that pelvic EBRT induces systemic increases in TNF-α and a decline in voluntary wheel running activity (VWRA) , an objective measure of sickness in mice. A specific aim of this study was to determine the requirement of EBRT for TNF-α for the induction of sickness behavior. Methods: Daily VWRA was monitored in male WT (n=10) and TNF-α−/− (n=10) anesthetized mice undergoing pelvic EBRT at 4.6 Gy/fraction, 5 days per week for 15 fractions for a total dose of 69 Gy [4.6 X 15 = 69, not 70]. Control WT (n=10) and TNF-α−/− (n= 10) mice underwent anesthesia followed by sham EBRT. The effect of treatment on weight and food intake was also determined by calculating change in weight and daily food intake during treatment. A 2 x 2 repeated measure analysis of covariance ANCOVA was used to determine whether there was a significant interaction between treatment group (EBRT or Control) and genotype (WT or TNF-α−/−) on voluntary wheel running activity controlling for baseline differences in this variable. Similarly a 2 x 2 ANOVA was used to determine whether there was a drug x genotype interaction between change in body weight or food intake. Results: There was a significant effect of EBRT on VWRA (p&lt; 0.001), food intake (p0.002), and weight (p&lt;0.001). We did not however observe a significant interaction between EBRT and genotype in VWRA (p= 0.756), food intake (p=0.654), or weight (p= 0.450). Conclusions: Targeting TNF-α using specific cytokine blocking agents has been suggested as a potential strategy for preventing or managing EBRT related fatigue. Although our prior data support that localized EBRT to the pelvis may induce TNF-α and sickness behavior in mice, our latest data do not support a direct role for this cytokine in mediating these effects.

Abstract B35: Serum inflammatory biomarkers of acute and persistent fatigue in a preclinical breast cancer treatment model

Abstract Aims: Cancer treatment related fatigue (CTRF) is a debilitating symptom of cancer chemotherapy. The acute CTRF that occurs during chemotherapy can become persistent lasting for weeks, month, or years after treatment has ended. Although, treatment-related increases in IL-1β and TNF-α have been implicated in CTRF, the role that these cytokines play in CTRF is unclear. The aim of this study was to determine the relationship between chemotherapy-induced IL-1β and TNF-α production and acute and persistent CTRF in a pre-clinical mouse model. Methods: Blood levels of IL-1β, TNF-α and several other inflammatory biomarkers were measured in acutely fatigued, non-fatigued, and persistently fatigued mice following administration of cytoxan-adriamycin-5-fluorouracil (CAF), a commonly used adjuvant chemotherapy regimen for the treatment of breast cancer, by assessing changes in voluntary wheel running activity as a proxy for fatigue. Results: Fatigued mice showed increased blood levels of IL-1β, TNF-α as well as several other inflammatory markers including, IL-5, IL-6, IL-7, IL-9, IP-10, G-CSF, KC, MCP-1 and MIP-1β. Importantly, serum levels of these fatigue associated biomarkers were not significantly increased in non-fatigued CAF treated mice. CAF-treated mice with persistent fatigue had elevated serum levels of IL-6, IL-17, and MIP-1α. Conclusions: This study advances the science of symptom management by providing evidence that treatment induced increases in IL-1β and TNF-α play a role in acute CTRF. Similar temporal analyses between serum inflammatory biomarkers in the clinical setting may lead to a better understanding of the role of immune dysfunction in the etiology of acute and persistent fatigue. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B35

Abstract A28: A murine model for cancer treatment-related fatigue

Abstract Objectives: Among patients being treated for cancer, cancer treatment-related fatigue (CTRF) remains a poorly understood condition with a profound effect on quality of life. Our objective was to develop a murine model of CTRF, independent of anemia, in order to further understand its pathogenesis and provide a conduit for the development of mechanistically-based therapeutic approaches. Methods: To determine the optimal dose of ionizing radiation to produce fatigue, female BALB/c mice were irradiated with 10 doses of fractionated total body irradiation (fTBI, 8, 9, and 10 Gy, cumulative dose) or 15 doses (fTBI, 10.5 and 13.5 Gy, cumulative dose). In a separate experiment, mice received 70, 60 or 50 mg/kg of etoposide sulfate to determine the optimal dose of chemotherapy to induce CTRF. Cage-top activity sensors (Phillips Respironics) were used to evaluate daily activity patterns in animals up to 4 weeks following the completion of radiation or 12 weeks following etoposide sulfate administration. CTRF was induced by 15 doses of fractionated total body irradiation (fTBI, 10.5 Gy, cumulative dose) in female BALB/c mice or 60mg/kg etoposide sulfate administered as a single dose. Total daily animal activity and changes in wake/sleep cycles were compared to baseline levels. Systemic levels of IL-6 and TNF-α were measured and anemia and leukopenia were assessed using specimens obtained in the weeks following the last dose of radiation or etoposide sulfate administration. Results: fTBI resulted in animals with a significantly lower cumulative daily activity, disrupted sleep/wake cycles that continued up to forty days following the last dose of radiation. Administration of etoposide sulfate resulted in a significantly lower cumulative daily activity three weeks following chemotherapy administration and continued for the duration of the study. Reduced activity levels were not associated with laboratory parameters suggestive of anemia. Changes in the measured hematological parameters demonstrated a temporal, dose-dependent and reversible pattern; consistent with those previously reported in human patients. Conclusions: Despite its frequency and impact, CTRF has been accepted as a cost of successful cancer treatment. This conclusion was largely based on the supposition that, aside for symptom control, there was no opportunity to develop an effective intervention. We report the development a novel mouse model of CTRF in which administration of fractionated TBI or etoposide sulfate was able to induce behaviors consistent with fatigue reported in humans. Our data supports the hypothesis that TBI and chemotherapy induce systemic effects that result in changes in daily activity patterns and sleep/wake cycles in the absence of anemia. Consistent with reports in humans with fatigue syndromes, radiation-induced CTRF correlated with increased levels of TNF and IL-6. Additional work is ongoing to further characterize the model. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A28.

Does Muscle-Derived Interleukin-6 Mediate Some of the Beneficial Effects of Exercise on Cancer Treatment-Related Fatigue?

To review evidence that muscle-derived interleukin-6 (IL-6) mediates some of the beneficial effects of exercise on cancer treatment-related fatigue (CTRF). Electronic nursing, psychology, and medicine databases. Fatigue is a common and often debilitating symptom associated with cancer treatment. Although the molecular mechanisms underlying CTRF have yet to be fully elucidated, it may be akin to the fatigue associated with "sickness behavior," which is initiated by the production of the proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). Physical exercise has been shown to decrease fatigue levels in patients with cancer undergoing treatment. Skeletal muscle selectively produces IL-6 during exercise, and muscle-derived IL-6 can decrease the production and activity of IL-1 beta and TNF-alpha. Thus, the anti-inflammatory effects of muscle-derived IL-6 may be a mechanism underlying the observed beneficial effects of exercise on CTRF. Further studies are needed to determine whether the anti-inflammatory effects of exercise underlie its beneficial effects on CTRF. Nurses have proven to be leaders in the field of cancer symptom management. An understanding of potential mechanisms underlying the beneficial effects of exercise on CTRF may help to fine-tune exercise interventions to maximize symptom control and to identify new treatment strategies for fatigued patients with cancer who are unable to participate in an exercise program.

Methodological Issues in the Investigation of Ginseng as an Intervention for Fatigue

Although literature suggests that fatigue is commonly reported by women during and after breast cancer treatment, treatment options are limited. Although ginseng is widely used in Asian countries as a tonic to increase energy, its efficacy for treating cancer-related fatigue has not been carefully studied. We conducted a pilot study to evaluate the feasibility of a larger clinical trial to investigate the efficacy of ginseng for treating breast cancer-related fatigue. Breast cancer survivors seeking treatment for fatigue were recruited to participate in an 8-week randomized, double-blind, placebo-controlled trial. A variety of practical problems were encountered in the study, including large numbers of survivors with conditions that were possible contraindications to ginseng use, inability to achieve blinding for the intervention because of strong odor from the ginseng, and measurement device failure. Evaluating ginseng for breast cancer treatment-related fatigue is a great challenge, particularly if a blinded randomized design is desired. This article provides insight into issues related to investigating complementary therapies and the importance of pilot studies for identifying methodological problems.

A neuroendocrine-based regulatory fatigue model.

To provide an overview of select existing fatigue models and propose a neuroendocrine-based regulatory fatigue model that can serve as a foundation for interventions to manage fatigue. Biobehavioral systems based on a neuroendocrine regulatory framework. Empirical data and literature review to develop a fatigue model to serve as a foundation for interventions to manage fatigue. The proposed model will facilitate testing of interventions based on the premise that common neuroendocrine transmitters provide the mechanisms of fatigue in patients diagnosed with chronic illnesses, such as with cancer treatment-related fatigue. The model may also be used to identify predictors of fatigue in specific patient populations, provide guidance for clinicians in their selection of precise interventions to be implemented, and identify the effects of treatments captured in these populations. By clearly identifying the mechanisms of fatigue, we can discover which interventions are effective for particular types of fatigue.

Fatigue in patients with cancer.

To provide a historic perspective on knowledge about fatigue in patients with cancer, review what is known, define gaps, and recommend future approaches. Published research reports, clinical papers, review articles, and practice guidelines. Two tested interventions show consistent positive effects: treatment of chemotherapy-induced anemia and aerobic exercise. Other frequently suggested interventions, such as adequate nutrition, energy conservation, psychostimulants, antidepressants, and increased sleep and rest, either have not been tested or studies underway are not yet complete. Current practice guidelines are based on a combination of research and expert clinical judgment. The knowledge base on fatigue continues to expand. Information about the mechanisms underlying fatigue is needed to develop innovative approaches to prevent and treat fatigue. Current practice guidelines should be used to guide care with the expectation that guidelines will evolve to incorporate the results of studies currently underway. Although specific gaps in knowledge need to be addressed to guide future practice, clinicians need to use existing knowledge in the care they are delivering today. All of the interventions proposed for managing cancer treatment-related fatigue are health policy challenges because they represent additions to usual care rather than replacements of existing components of care.

The trajectory of fatigue in adult patients with breast and ovarian cancer receiving chemotherapy.

To describe the trajectory of fatigue and determine the feasibility of exploring physiologic mechanisms of fatigue in adult patients receiving chemotherapy for breast and ovarian cancer. Descriptive, longitudinal, repeated measures. Outpatient ambulatory cancer centers within two large, academic, teaching hospitals with overnight hospital stays in general clinical research centers. Seventeen adult participants with either early-stage breast or ovarian cancer receiving chemotherapy for the first time. Demographic questionnaire; Piper Fatigue Scale (PFS); hemoglobin, bilirubin, melatonin, and weight change were measured at baseline, three months, and approximately six months. PFS also was collected at three additional two-week nadir, post-treatment, measurement points. Descriptive statistics and repeated analysis of variance measures were used to analyze data. Fatigue, hemoglobin, bilirubin, melatonin, and presence of other comorbid disease. Subjective fatigue was experienced by the majority of patients receiving chemotherapy. It was irregular over time, intensified at three months, and continued after treatment ended. The physiologic trajectory of fatigue from baseline to three months indicated a significant change over time in hemoglobin in the breast cancer group (p = 0.02) and in nighttime melatonin levels for both breast and ovarian cancer groups (p = 0.03). Although not significant, daytime melatonin levels changed over time from baseline to six months. Fatigue fluctuates during the course of chemotherapy treatment and does not cease after treatment ends. Preliminary findings suggest that fatigue mechanisms may have an undetermined physiologic basis. Assessment of cancer treatment-related fatigue must be ongoing, even after treatment ends. Findings suggest an awareness of the importance of understanding fatigue mechanisms to enable future testing of research-based interventions.