A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer (original) (raw)
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Multitargeted Treatment of Cancer Cachexia
Critical Reviews™ in Oncogenesis, 2012
Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The prominent clinical feature of cachexia is weight loss in adults. Anorexia, inflammation, insulin resistance, and increased muscle protein breakdown frequently are associated with cachexia. One single therapy may not be completely successful in the treatment of cachexia because of the complexity of the pathogenesis and symptoms of the cachexia syndrome. Among effective treatments, progestogens currently are considered the best available treatment option and are the only approved drugs in Europe for the treatment of cancer-and AIDS-related cachexia. However, they have limited efficacy in treating cancer cachexia. However, thalidomide, selective COX-2 inhibitors, ghrelin mimetics, and selective androgen receptor modulators showed promising results but should be defined further and confirmed in clinical trials. Therefore, to date, despite several years of coordinated efforts in basic and clinical research, the practice guidelines for the prevention and treatment of cancer-related anorexia cachexia syndrome (CACS) are lacking. The management of CACS is a complex challenge that should address the different causes underlying this clinical event. Recent studies showed that integrated, multitargeted approaches are more effective than single-agent approaches for the treatment of CACS. Further clinical trials to improve and refine current strategies to counteract cancer cachexia using multimodal interventions, including nutritional supplementation, anabolic agents, and antiinflammatory drugs along with an appropriate physical exercise program, are warranted. KEY WORDS: cancer cachexia, multitargeted approach, lean body mass, physical activity, quality of life ABBREVIATIONS CACS: cancer-related anorexia cachexia syndrome; REE: resting energy expenditure; TNF: tumor necrosis factor; IL: interleukin; ROS: reactive oxygen species; CRP: C-reactive protein; MPA: medroxyprogesterone acetate; LBM: lean body mass; SIMS: systemic immune metabolic syndrome
Comparison of three different treatment modalities in the management of cancer cachexia
Tumori Journal, 2013
Aims and background. The optimal treatment of cancer cachexia remains unknown. In this study, we compared the efficacy of three different treatment modalities in the management of cancer cachexia. Methods. Sixty-two assessable cachectic cancer patients were randomized to one of the following three arms: 1) megesterol acetate (MA) plus meloxicam (n = 23); 2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement (n = 21); or 3) meloxicam plus oral EPA-enriched nutritional supplement (n = 18). Treatment duration was 3 months. Results. The treatment arms were well balanced at baseline. The primary efficacy (body weight and lean body mass) and secondary efficacy (body mass index, quality of life, and serum levels of IL-6 and TNF-α) parameters improved after treatment in all three arms. There were no statistically significant differences between treatment groups in the mean percentage changes in all efficacy parameters from baseline to end of study. Conclusions. MA plus meloxicam or EPA supplement plus meloxicam may be effective treatment options in the management of cancer cachexia. The combined use of these agents does not provide further advantages.
BMJ supportive & palliative care, 2018
Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment. Following a successful phase II trial, a phase III randomised controlled trial of a multimodal cachexia intervention is under way. Termed the MENAC trial (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia), this intervention is based on evidence to date and consists of non-steroidal anti-inflammatory drugs and eicosapentaenoic acid to reduce inflammation, a physical exercise programme using resistance and aerobic training to in...
Management of Cancer Cachexia: ASCO Guideline
Journal of Clinical Oncology
PURPOSE To provide evidence-based guidance on the clinical management of cancer cachexia in adult patients with advanced cancer. METHODS A systematic review of the literature collected evidence regarding nutritional, pharmacologic, and other interventions, such as exercise, for cancer cachexia. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and systematic reviews of RCTs published from 1966 through October 17, 2019. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS The review included 20 systematic reviews and 13 additional RCTs. Dietary counseling, with or without oral nutritional supplements, was reported to increase body weight in some trials, but evidence remains limited. Pharmacologic interventions associated with improvements in appetite and/or body weight include progesterone analogs and corticosteroids. The other evaluated interventions either had no benefit or insufficient evidence of benefit t...
Revisiting Cancer Cachexia: Pathogenesis, Diagnosis, and Current Treatment Approaches
2021
The objective of this article is to group together various management strategies and to highlight the recent treatment modifications that attempt to target the multimodal etiological factors involved in cancer cachexia. The contemporary role of nursing fraternity in psychosocial and nutritional assessment of cancer patients is briefly discussed. Cachexia is a syndrome of metabolic disturbance, characterized by the inflammation and loss of muscle with or without loss of adipose tissue. In cancer cachexia, a multifaceted condition, patients suffer from loss of body weight that leads to a negative impact on the quality of life and survival of the patients. The main cancers associated with cachexia are that of pancreas, stomach, lung, esophagus, liver, and that of bowel. The changes include increased proteolysis, lipolysis, insulin resistance, high energy expenditure, and reduced intake of food, all leading to impaired response to different treatments. There is no standardized treatment...
Outcomes of novel trials for cancer cachexia
Clinical Investigation, 2014
Cancer cachexia is a multifactorial syndrome characterized by involuntary loss of skeletal muscle and fat, reduced quality of life and decreased survival. Unlike starvation, weight loss cannot be fully reversed by increasing caloric intake. Interventions, such as nutritional counseling or currently available appetite stimulants such as megestrol acetate have limited benefits. Recently, there has been an increase in the understanding of the pathophysiology contributing to weight loss in patients with cancer. Clinical trials of various pharmacological therapies targeting the underlying pathophysiological derangements contributing to cancer cachexia are underway. A personalized approach may be needed for managing patients with anorexia-cachexia syndrome in conjunction with the best supportive care. The following narrative review will highlight novel therapies being investigated for the treatment of cancer cachexia, which can be used as a single-agent or combined in multimodal therapy.
Nutritional Interventions to Improve Cachexia Outcomes in Cancer—A Systematic Review
Medicina
Background and Objectives: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of nutritional interventions aiming to improve cachexia outcomes in cancer, focusing on weight gain. Materials and Methods: A search in Medline and Elsevier databases for articles up until the 23 January 2022, was conducted. Results: Out of 5732 screened records, 26 publications were included in the final analysis. Four randomized clinical trials showed a significant body weight (BW) increase in patients treated with eicosapentaenoic acid (EPA), β-hydroxy-beta-methyl butyrate (β-HMB), arginine, and glutamine or marine phospholipids (MPL). An upward BW trend was observed in patients treated with L-carnitine, an Ethanwell/Ethanzyme (EE) regimen enriched with ω-3 fatty acids, micronutrients, probiotics, fish oil, a leucine-rich supplement, or total parental nutrition (TPN) with a high dose of a branched...
Cancer Cachexia: Beyond Weight Loss
Journal of oncology practice, 2016
Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is...