Exercise and side effects among 749 patients during and after treatment for cancer: a University of Rochester Cancer Center Community Clinical Oncology Program Study

Goals Despite advances in cancer treatment and symptom management, many patients experience side effects from cancer treatments that cause suffering and impair quality of life (QOL). Exercise is a method for enhancing QOL among cancer patients that shows promise in reducing side effects. However, patient participation in exercise is not well defined. We report on exercise participation during and within 6 months after chemotherapy and radiation therapy, the association of exercise with treatment side effects, and the communication between physicians and patients about exercise in a large (N=749) nationwide sample of cancer patients.Patients and Methods Participants completed measures that included questions concerning exercise during and after treatment, treatment side effects, and communication with physicians regarding exercise. Questionnaires were administered 2 weeks and 6 months after completion of therapy.Results Almost half of the 749 participating patients reported exercising while undergoing chemotherapy and/or radiation, and more than half reported exercising during the 6 months after treatment. Exercise was associated with less severe side effects during and after treatment (p≤0.050). More than 30% of patients reporting exercise did not discuss exercise with a physician; however, those who did were more likely to talk with their oncologist than with their primary care provider.Conclusions Cancer patients report exercising and appear amenable to attempting exercise during and within 6 months after treatment. Research is needed to assess (1) the frequency, intensity, duration, and mode of exercise; (2) randomized controlled trials with exercise and its influence on treatments and side effects; and (3) physician–patient communication regarding exercise during cancer treatment.     

Cachexia and anorexia: cancer's covert killer

 Cachexia and anorexia are often not observed at the time of diagnosis of cancer. While the initial medical intervention for cancer patients includes antitumor therapy and pain management, the consequences of cachexia and anorexia may be ignored, to the detriment of the patient's quality of life and his or her potential response to chemotherapy. The importance of a well-defined therapeutic strategy to treat cachexia is in order if the patient's overall wellbeing is to improve. Presented is a review of the pharmacological management of anorexia and cachexia, including a four-step ladder approach to medical management. Published online: 13 March 2000     

Understanding cachexia and excessive weight loss in cancer

Cachexia, a wasting condition often seen in advanced cancer, is often confused with anorexia but they are two separate conditions. It is evident that cachexia frequently leads to anorexia but anorexia alone cannot cause cachexia. The cachexia syndrome is weight loss with a specific cause--the action of cytokines, chemical messengers that are produced both by the body in response to the tumour and by the tumour to ensure its growth and spread. Treatment of cachexia is very difficult. Drugs to improve appetite have little effect, however, supplementing the diet with fish oils and vitamin E seems to be beneficial. Increasing a patient's level of exercise, even if bed-bound, does seem to have a positive effect and helps to synthesize skeletal muscle protein and delay the ravages of cachexia. Increasing exercise also has a positive effect on fatigue levels, a side-effect of cachexia.     

Anorexia–Cachexia syndrome in cancer: implications of the ubiquitin–proteasome pathway

Introduction Malnutrition is a common problem in cancer patients. Its incidence varies according to disease stage (between 15 and 90%) and is considered a possible prognostic factor for therapeutic response and survival. It is also one of the causes contributing to the increase in morbidity and mortality in patients. Tumor cachexia is defined as a nutritional defect caused by tumor growth in the patient and presents as a significant weight loss. This weight loss is mainly caused by a degradation of skeletal muscle proteins.Conclusion The ubiquitin–proteasome system is the most important pathway of protein degradation. As a regulatory system governing protein half-life, it is involved in the regulation of the cell cycle, signal transmission, immune system response, apoptosis, and oncogenesis. Knowledge of the molecular pathways involved in the induction of cancer-associated cachexia will favor a more rational approach to its treatment as well as possible quality of life and survival benefit for the patient.     

A systematic review of health-related quality of life instruments in patients with cancer cachexia

Purpose

Assessing the health-related quality of life (HRQOL) of cancer patients with cachexia is particularly important because treatments for cachexia are currently aimed at palliation and treatment efficacy must be measured in ways other than survival. The aim of this systematic review was to evaluate HRQOL assessment in cancer patients with cachexia.

Methods

Using guidance from the Centre for Reviews and Dissemination, relevant databases were searched from January 1980 to January 2012 with terms relating to cancer, cachexia and HRQOL for papers including adult cancer patients with cachexia or documented weight loss at baseline.

Results

We found one cachexia-specific instrument, the Functional Assessment of Anorexia/Cachexia Therapy, but the tool has not been fully validated, does not cover all the relevant domains and the consensus-based standards for the selection of health status measurement instruments checklist highlighted a number of weaknesses in the methodological quality of the validation study. Sixty-seven studies assessed HRQOL in cachectic or weight-losing cancer patients. Most used generic cancer HRQOL instruments, limiting the amount of useful information they provide. A modified version of the Efficace minimum data checklist demonstrated that the quality of reporting on HRQOL tool use was inadequate in many of the studies. A negative relationship between HRQOL and weight loss was found in 23 of the 27 studies which directly examined this.

Conclusion

There is a pressing need for a well-designed HRQOL tool for use with this patient group in both clinical trials and clinical practice.     

Nutritional support in multimodal therapy for cancer cachexia

Introduction Malnutrition has since long been known to be associated with adverse outcomes in cancer patients. The wasting in cancer cachexia involves loss of muscle and fat and reflects a catabolic metabolism induced by an abnormal host response to tumour presence and/or tumour factors. Patients with cancer cachexia frequently develop a chronic negative energy and protein balance driven by a combination of reduced food intake and metabolic change. Thus, alterations in both energy intake and components of energy expenditure may contribute to progressive weight loss. Increased resting energy expenditure related to the systemic inflammatory response is common and a sustained hypermetabolism over a long period of disease progression can make a large contribution to negative energy balance and wasting if not compensated for by an increase in energy intake. Hypermetabolism and diminished energy intake due to anorexia may thus constitute a vicious circle in the development of cancer cachexia. Discussion Though nutritional support alone can improve energy intake to a variable extent and for a variable period of time, it will not address the underlying catabolic metabolism and is thus likely to be of limited efficacy if attempts to attenuate the tumour-induced catabolic response are not carried out at the same time. Concomitant drug treatments for cancer cachexia may slow down the wasting process by reducing anorexia, attenuating the systemic inflammation, the skeletal muscle catabolism or stimulating the muscle protein anabolism. Thus, improved management of cancer cachexia may require a multimodal approach by a multi-disciplinary team and is best commenced earlier rather than later. Early start of therapy also facilitates the use of oral nutritional supplementation, which is preferable to parenteral nutrition in the majority of cases. Once a patient is severely wasted it may be neither practical nor ethical to intervene with anything else than supportive care. Conclusion An improvement in the condition of all patients with cachexia may not be possible, however, the goal must be to stabilise cachexia and prevent or delay further decline. There is currently no single or combined treatment strategy which is successful in all patients. However, strategies to counteract both hypermetabolism and reduced dietary intake have been demonstrated to be of importance for the survival, function and quality of life of cancer patients and should be further explored in interventional studies. Presented as invited lecture at the MASCC/ISOO 20th Anniversary International Symposium Supportive Care in Cancer in St. Gallen, June 2007.     

Cancer-induced fatigue and skeletal muscle wasting: the role of exercise

Fatigue is the most frequently reported symptom by cancer patients. Many of these patients perceive fatigue as the most distressing symptom associated with their illness because it imposes limitations on their physical activity level. Skeletal muscle wasting, which occurs as part of cancer cachexia, is one of the mechanisms that contribute to fatigue. Cancer-induced skeletal muscle wasting may occur despite normal food intake and is not prevented by nutritional supplementation. Evidence suggests that endurance exercise ameliorates cancer-related fatigue. There is no compelling evidence to support that exercise-induced reduction in fatigue is related to preservation of muscle mass. Resistance exercise attenuates muscle wasting associated with a variety of catabolic conditions. However, its effects on cancer-induced muscle wasting have not been adequately studied. This article describes the physiological mechanisms implicated in the induction of cancer-related muscle wasting, summarizes findings from endurance and resistance exercise studies in relation to fatigue and muscle wasting during cancer and selected clinical conditions, and proposes directions for future research.     

Management of cancer cachexia

The diagnosis of cancer has traditionally been associated with malnutrition and wasting. Oncology patients are at risk for nutrition-related problems because of the cancer itself, as well as the treatment prescribed. Clinical manifestations of cachexia include anorexia, weight loss, muscle wasting, and fatigue, resulting in poor performance status. Control of symptoms, such as anorexia, nausea and vomiting, and mucositis is imperative in the management of cancer cachexia. Current pharmacologic therapies, as well as complementary and alternative methods, are presented. The nurse plays a key role in ensuring that the nutritional needs of oncology patients are met.     

Characterization of the Yoshida sarcoma: a model of cancer cachexia

Purpose

Cancer cachexia contributes significantly to morbidity and mortality in individuals with cancer. Currently, the mechanisms contributing to the development of cachexia are largely unknown, leading to a paucity of treatment and prevention options. Animal models are necessary in determining causal mechanisms and in testing potential treatments. While the Yoshida sarcoma has been utilized for more than 50 years, the cachexia syndrome produced by this model has not been well characterized in the literature.

Methods

Tumor allografts were subcutaneously implanted in male Sprague Dawley rats (n?=?16) and allowed to grow for 23 days. Control animals (n?=?16) received a sham surgery. All rats were monitored daily for the presence of hallmark cachexia symptoms.

Results

The results demonstrate the presence of decreased body weight gain, as well as lower levels of body adiposity and skeletal muscle mass, in tumor-bearing animals, as compared to controls.

Conclusions

While a large tumor burden was reached, the extent of cachexia was similar to that which is observed in many individuals with cancer cachexia. Future experiments utilizing this model are encouraged to identify mechanisms and effective treatment and prevention strategies.     

Cannabinoide in der Palliativtherapie des Anorexie-Kachexie-Syndroms

Loss of appetite and cachexia are frequent symptoms in palliative care patients. However, therapeutic regimens often prove ineffective, and the quality of life of many patients is significantly impaired by these symptoms. Causes and pathophysiology of anorexia and cachexia are complex and must be identified and treated. Symptomatic pharmacological therapy aims at metabolic, neuroendocrinological and catabolic changes. Prokinetic drugs, corticosteroids and gestagenes are used for symptomatic therapy. Recently, the use of cannabinoids for treatment of loss of appetite and cachexia has become the focus of interest. In cancer patients, cannabinoids proved more effective than placebo but less than gestagenes. Compared to placebo, higher efficacy of cannabinoids could be demonstrated in patients with AIDS as well as in patients with Morbus Alzheimer. However, side effects, such as dizziness, tiredness and daze led to discontinuation of the cannabinoid therapy in some patients.     

Cancer cachexia: a therapeutic approach

Cancer cachexia is a complex syndrome which occurs in more than two-thirds of patients who die with advanced cancer. The main components of this pathological state are anorexia and metabolic abnormalities such as glucose intolerance, fat depletion, and muscle protein catabolism among others. The aim of the present study is to review the different therapeutic approaches that have been designed to fight and counteract cancer cachexia.     

Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial

After a 3-month, single-blind, run-in period, 151 patients with intermittent claudication were randomly allocated to receive the antiplatelet agent ticlopidine (250 mg twice per day) or an identical placebo. One hundred and twenty patients completed the double-blind phase of the trial, which lasted 21 months. The primary analysis was performed according to the "intention-to-treat principle" in all 151 enrolled patients. There was, continuing on from the third month after randomization, a progressive and sustained improvement of the pain-free and maximum walking distances in the two treatment groups that was significantly greater in the ticlopidine group. The ankle-arm systolic blood pressure ratio at rest and after exercise increased in a significant manner in the ticlopidine group only. In a secondary analysis, with exclusion of 25 patients because of protocol violations at selection, consistently significant differences in favor of the ticlopidine group were still observed for maximum walking distance and systolic ankle-arm blood pressure ratio, both at rest and after exercise. No major side effects were reported in the treated group. It is concluded that long-term treatment with ticlopidine improves walking ability and ankle systolic blood pressure in patients with claudication.     

Exercise interest and preferences among patients diagnosed with primary brain cancer

Goals of the work The purpose of the present investigation was to examine the interest and exercise preferences of an institution-based sample of brain tumor patients. Secondary aims were to examine potential differences in participant’s interest and preferences by exercise behavior and select demographic/medical variables. Materials and methods Using a cross-sectional design, 106 brain tumor patients (age range, 32 to 83 years) who received treatment at the Preston Robert Tisch Brain Tumor Center (BTC) at Duke completed a questionnaire that assessed self-reported exercise behavior, exercise interest and preferences during active and off-treatment periods. Main results For exercise program preferences, participants were significantly more interested and felt more capable of participating in an exercise program following compared to during adjuvant therapy. Approximately equal proportions of brain tumor patients preferred to exercise at home with their spouse or other family members. These preferences were consistent across both cancer treatment-related time periods. For exercise information preferences, a higher proportion of respondents preferred receiving information via technologically based approaches (i.e., Internet, CD-ROM, and mailed correspondence) compared with more traditional methods (i.e., mail or face-to-face counseling). Chi-square analyses revealed that a small number of exercise program and information preferences were modified by exercise, medical, and demographic variables. Conclusions Brain tumor patients may have unique and varied preferences compared with other cancer populations. Incorporating patient’s preferences into rehabilitation programs and clinical exercise investigations may optimize the potential benefits of this modality for patients with neurologic malignancies.     

Safety,Effectiveness, and Uptake of Exercise Medicine Integrated Within a Cancer Care Center

ObjectivesThe aim of this study was to evaluate the safety, effectiveness, and acceptability of an exercise clinic co-located within a cancer treatment center to identify best practices for integrating exercise medicine into cancer care.Data SourcesTwo-hundred thirty-seven patients were referred to the exercise clinic and completed self-report health and demographic questionnaires. Further assessments were conducted at baseline on 67 patients and following completion of the exercise program by 46 patients. Endpoints included muscular strength, physical function, cardiorespiratory fitness, body composition, quality of life, and fatigue scores. Adverse events were tracked throughout exercise participation to evaluate program safety.ConclusionExercise programming co-located and aligned with cancer treatment in a real-world clinical setting appears to be safe with only four minor exercise-related adverse events. Effectiveness was demonstrated by all physical performance (2.9%–9.5%), strength (7.4%–27.6%), and balance (10.1%) improving and some patients reported outcomes exhibiting modest but clinically relevant benefit. Importantly, no outcomes including fatigue worsened even though the patients were undergoing radiation and/or chemotherapy. Assessment of patient physical and self-reported outcomes should be co-located where they receive oncological treatment and/or exercise medicine to increase uptake of this aspect of the service. Future work should incorporate and describe program and implementation design to help identify best practices in exercise oncology programming.Implications for Nursing PracticeNurses are a primary driver of exercise among patients receiving treatment for cancer. Their regular patient interactions offer a practical opportunity to collect and record important exercise-related information from patients. As organizations look to develop plans to implement exercise into standard practice, input from nurses is critical to ensure program feasibility.     

The Systemic Theory of Living Systems and Relevance to CAM: The Theory (Part II)

This theory stems from observing the universe's ‘omniscient’nature, manifested in flows of energy and information of itslife plethora. A notorious example is the living cell's intelligentnature, which guides its basic goal: to maximize survival. Thislast motivated me to address the living system's intelligence,which constitutes a vital and controversial topic, its relationshipwith ‘incurable’ disease in general, including cancer,and to propose golden rules for therapeutics, as well as a definitionof ideal medicine. The scientific confirmation of these findingsis embedded in discoveries in cybernetics, biological theoryof information and modern thermodynamic concepts, concerningenergy and information exchange, within a living system. Thisapproach's practical application, denominated Systemic Medicine,has been substantiated by treatment and results obtained in>300 000 patients suffering from chronic degenerative diseases.     

Physical activity level as an outcome measure for use in cancer cachexia trials: a feasibility study

Purpose  

Cancer cachexia impacts on treatment options, quality of life and survival. New treatments are emerging but need to be assessed using outcomes which patients find meaningful. One approach is the measurement of physical activity levels by small lightweight monitors, but experience is limited in cancer patients.     

Traditional and Modern Biomedical Prospecting: Part II-the Benefits: Approaches for a Sustainable Exploitation of Biodiversity (Secondary Metabolites and Biomaterials from Sponges)

The progress in molecular and cell biology has enabled a rationalexploitation of the natural resources of the secondary metabolitesand biomaterials from sponges (phylum Porifera). It could beestablished that these natural substances are superior for biomedicalapplication to those obtained by the traditional combinatorialchemical approach. It is now established that the basic structuraland functional elements are highly conserved from sponges tothe crown taxa within the Protostomia (Drosophila melanogasterand Caenorhabditis elegans) and Deuterostomia (human); therefore,it is obvious that the molecular etiology of diseases withinthe metazoan animals have a common basis. Hence, the major challengefor scientists studying natural product chemistry is to elucidatethe target(s) of a given secondary metabolite, which is perse highly active and selective. After this step, the potentialclinical application can be approached. The potential valueof some selected secondary metabolites, all obtained from spongesand their associated microorganisms, is highlighted. Examplesof compounds that are already in medical use (inhibition oftumor/virus growth [arabinofuranosyl cytosine and arabinofuranosyladenine]), or are being considered as lead structures (actingas cytostatic and anti-inflammatory secondary metabolites [avarol/avarone],causing induction of apoptosis [sorbicillactone]) or as prototypesfor the interference with metabolic pathways common in organismsranging from sponges to humans (modulation of pathways activatedby fungal components [aeroplysinin], inhibition of angiogenesis[2-methylthio-1,4-napthoquinone], immune modulating activity[FK506]) are discussed in this study. In addition, bioactiveproteins from sponges are listed (antibacterial activity [pore-formingprotein and tachylectin]). Finally, it is outlined that theskeletal elements—the spicules—serve as blueprintsfor new biomaterials, especially those based on biosilica, whichmight be applied in biomedicine. These compounds and biomaterialshave been isolated/studied by members of the German Center ofExcellence BIOTECmarin. The goal for the future is to successfullyintroduce some of these compounds in the treatment of humandiseases in order to raise the public awareness on the richnessand diversity of natural products, which should be sustainablyexploited for human benefit.     

Rapid progression of advanced "hormone-resistant" prostate cancer during palliative treatment with progestins for cancer cachexia

We report three patients with advanced "hormone-resistant" prostate cancer, each of whom had rapid progression of the disease during treatment with megestrol acetate for cancer cachexia. All patients had been previously treated with total androgenic deprivation. With progression of the disease, megestrol acetate was given to palliate the cancer-related wasting syndrome. No other antineoplastic drugs were contemporaneously given, and no concomitant condition that could favor the progression of the disease was present. The worsening observed while receiving megestrol acetate, and the atypical withdrawal syndrome occurring after the treatment was stopped, seem to suggest a promoting role of megestrol acetate in advanced "hormone-resistant" prostate cancer. The risk of rapid disease progression overwhelming the anti-cachectic palliative effect should be kept in mind when progestins are administered as a palliative treatment of cancer cachexia in patients with advanced "hormone-resistant" prostate cancer.     

The biochemical basis of metabolism in cancer cachexia.

Cancer cachexia is a syndrome of progressive body wasting characterized by loss of adipose tissue and skeletal muscle mass. It is the most common side effect of malignancy occurring in approximately one-half of untreated cancer patients. The pathophysiology of cancer cachexia is not fully understood; however, studies have shown that cytokines are important in the alteration of carbohydrate, lipid, and protein metabolism. This leads to a shorter survival time and a decreased response to therapy. Cachexia is often found before any signs or symptoms of the cancer. An uncertainty with cachexia is whether nutritional support is feeding the patient or the tumor. Often, cachexia is not responsive to simple nutritional interventions. Furthermore, appetite stimulants, cytokine inhibitors, and Cori cycle inhibitors have been used to treat cancer cachexia.     

癌性恶病质诊断、评估及治疗进展

癌性恶病质是一类复杂的代谢综合征,包括肌肉消耗、脂肪消耗、非计划的体质量下降、厌食和免疫功能破坏等。恶病质可显著降低肿瘤患者的抗肿瘤治疗疗效,增加治疗毒副反应,加重患者的症状负担,影响患者的生活质量,并最终缩短患者的生存时间。本文将对癌性恶病质的诊断、临床评估以及治疗的研究进展进行综述。