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Justin C Brown, Elizabeth M Cespedes Feliciano, Bette J Caan
There is growing interest from the oncology community to understand how body composition measures can be used to improve the delivery of clinical care for the 18.1 million individuals diagnosed with cancer annually. Methods that distinguish muscle from subcutaneous and visceral adipose tissue, such as computed tomography (CT), may offer new insights of important risk factors and improved prognostication of outcomes over alternative measures such as body mass index. In a meta-analysis of 38 studies, low muscle area assessed from clinically acquired CT was observed in 27...
January 13, 2019: Journal of Cachexia, Sarcopenia and Muscle
Jimi S Malik, Sriram Yennurajalingam
Cancer cachexia (CC) is one of the most distressing syndromes for both patients and their families. CC can have an impact on patient reported quality of life and overall survival. It is often associated with symptoms such as fatigue, depressed mood, early satiety, and anorexia. Prokinetic agents have been found to improve chronic nausea and early satiety associated with CC. Among the prokinetic agents, metoclopramide is one of the best studied medications. The role of the other prokinetic agents, such as domperidone, erythromycin, haloperidol, levosulpiride, tegaserod, cisapride, mosapride, renzapride, and prucalopride is unclear for use in cachectic cancer patients due to their side effect profile and limited efficacy studies in cancer patients...
November 5, 2018: Annals of Palliative Medicine
Shailesh M Advani, Pragati G Advani, Helena M VonVille, Syed H Jafri
BACKGROUND: Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia...
November 27, 2018: BMC Cancer
David C Currow, Matthew Maddocks, David Cella, Maurizio Muscaritoli
Cancer cachexia is a multilayered syndrome consisting of the interaction between tumor cells and the host, at times modulated by the pharmacologic treatments used for tumor control. Key cellular and soluble mediators, activated because of this interaction, induce metabolic and nutritional alterations. This results in mass and functional changes systemically, and can lead to increased morbidity and reduced length and quality of life. For most solid malignancies, a cure remains an unrealistic goal, and targeting the key mediators is ineffective because of their heterogeneity/redundancy...
November 5, 2018: International Journal of Molecular Sciences
Michael I Ramage, Richard J E Skipworth
PURPOSE OF REVIEW: Randomized clinical trials of cancer cachexia interventions are based on the premise that an increase in the muscle mass of patients is associated with consequent improvements in muscle function, and ultimately, quality of life. However, recent trials that have succeeded in demonstrating increases in lean body mass have been unable to show associated increases in patient physical function. In this review, we examine the potential causes for this lack of association between muscle mass and function in cancer cachexia, paying particular attention to those factors that may be at play when using body composition analysis techniques involving cross-sectional imaging...
December 2018: Current Opinion in Supportive and Palliative Care
Fangyuan Zhang, Aomei Shen, Yinghui Jin, Wanmin Qiang
BACKGROUND: Cancer-related anorexia remains one of the most prevalent and troublesome clinical problems experienced by patients with cancer during and after therapy. To ensure high-quality care, systematic reviews (SRs) are seen as the best guide. Considering the methodology quality of SRs varies, we undertook a comprehensive overview, and critical appraisal of pertinent SRs. METHODS: Eight databases (between the inception of each database and September 1, 2017) were searched for SRs on the management of cancer-related anorexia...
August 9, 2018: BMC Complementary and Alternative Medicine
Megumi Morimoto, Katsuji Aikawa, Takahito Hara, Masuo Yamaoka
Cancer cachexia is a syndrome that impairs the quality of life and overall survival of patients, and thus the effectiveness of anticancer agents. There are no effective therapies for cancer cachexia due to the complexity of the syndrome, and insufficient knowledge of its pathogenesis results in difficulty establishing appropriate animal models. Previously, promising results have been obtained in clinical trials using novel agents including the ghrelin receptor agonist anamorelin, and the selective androgen receptor modulator (SARM) enobosarm to treat cachexia in patients with cancer...
December 2017: Oncology Letters
Nobuyuki Katakami, Junji Uchino, Takuma Yokoyama, Tateaki Naito, Masashi Kondo, Kouzo Yamada, Hiromoto Kitajima, Kozo Yoshimori, Kazuhiro Sato, Hiroshi Saito, Keisuke Aoe, Tetsuya Tsuji, Yuichi Takiguchi, Koichi Takayama, Naoyuki Komura, Toru Takiguchi, Kenji Eguchi
BACKGROUND: Cachexia, described as weight loss (mainly in lean body mass [LBM]) and anorexia, is common in patients with advanced cancer. This study examined the efficacy and safety of anamorelin (ONO-7643), a novel selective ghrelin receptor agonist, in Japanese cancer patients with cachexia. METHODS: This double-blind clinical trial (ONO-7643-04) enrolled 174 patients with unresectable stage III/IV non-small cell lung cancer (NSCLC) and cachexia in Japan. Patients were randomized to daily oral anamorelin (100 mg) or a placebo for 12 weeks...
February 1, 2018: Cancer
Kenichi Nishie, Shuhei Yamamoto, Chie Nagata, Tomonobu Koizumi, Masayuki Hanaoka
INTRODUCTION: Cancer anorexia-cachexia syndrome (CACS) is characterized by involuntary weight loss. CACS is commonly observed in advanced non-small-cell lung cancer (NSCLC), and it leads to a poor quality of life (QOL). No effective standard treatment exists for this condition. However, anamorelin has reportedly caused improvement in patients with several cancers. MATERIALS AND METHODS: We conducted a quantitative meta-analysis to explore the efficacy of anamorelin for treating CACS in patients with NSCLC...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Jose M Garcia
PURPOSE OF REVIEW: In spite of its relevance, treatments for the cancer anorexia and cachexia syndrome (CACS) are not available. One of the agents that recently reached phase III clinical trials is anamorelin. Its development, along with that of other agents for this indication, will be reviewed here, with a focus on the gaps in the current knowledge and future directions. RECENT FINDINGS: In spite of several targets showing promising results in early development, their difficulties obtaining regulatory approval underscore the need to reconsider the current strategies in drug development and the challenges in the field of CACS...
December 2017: Current Opinion in Supportive and Palliative Care
Eric Prommer
BACKGROUND: Cancer cachexia is a catabolic syndrome associated with uncontrolled muscle breakdown. There may be associated fat loss. Occurring in high frequency in advanced cancer, it is an indicator of poor prognosis. Besides weight loss, patients experience a cluster of symptoms including anorexia, early satiety, and weakness. The 3 stages of cachexia include stages of precachexia, cachexia, and refractory cachexia. Refractory cachexia is associated with active catabolism or the presence of factors that make active management of weight loss no longer possible...
2017: Palliative Care
Solomon A Graf, Jose M Garcia
Cancer anorexia-cachexia syndrome (CACS) is a complex and largely untreatable paraneoplastic complication common in advanced cancer. It is associated with profoundly deleterious effects on quality of life and survival. Since its discovery over a decade ago, anamorelin hydrochloride (anamorelin), a mimetic of the growth hormone secretagogue ghrelin, has shown considerable promise in ameliorating components of CACS when administered to patients with advanced cancer, including loss of lean body mass and reversal of anorexia...
2017: Drug Design, Development and Therapy
Jennifer G Le-Rademacher, Jeffrey Crawford, William J Evans, Aminah Jatoi
Most advanced cancer patients suffer loss of appetite (anorexia) and loss of weight. Despite the fact that cancer anorexia and weight loss are associated with a poor prognosis and detract from quality of life, no interventions have been demonstrated to palliate this syndrome in its entirety, particularly in patients with treatment-refractory malignancies. Recently, two registration trials - one with anamorelin and another with enobosarm - failed to reach their primary endpoints, thus raising questions. Were both these agents ineffective? Alternatively, did study design issues compromise the ability of these trials to identify effective agents? Thus, this review is timely insofar it serves as an introduction to study design, offers guidance on how to test promising agents for cancer anorexia/weight loss, and provides advice for overcoming trial design obstacles...
September 2017: Critical Reviews in Oncology/hematology
David C Currow, Richard Je Skipworth
Cancer cachexia affects many patients with advanced cancer. This multifactorial syndrome, which involves loss of muscle mass and body weight, profoundly affects patients' physical functioning and quality of life. Pharmacologic interventions that target weight loss and also improve patient-reported measures are required. Anamorelin hydrochloride is an oral ghrelin receptor agonist for the treatment of cancer anorexia-cachexia that stimulates release of growth hormone and insulin-like growth factor 1, and improves food intake and body weight...
August 2017: Future Oncology
D Currow, J S Temel, A Abernethy, J Milanowski, J Friend, K C Fearon
Background: Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities. Patients and methods: ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia...
August 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Yu Bai, Yunxia Hu, Yanhua Zhao, Xizhong Yu, Junwei Xu, Zhiyun Hua, Zhiqiang Zhao
PURPOSE: The aim of this study was to evaluate the therapeutic effects of Anamorelin on patients with cancer anorexia-cachexia syndrome (CACS) based on a meta-analysis of published randomized trials. METHODS: We searched PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials databases. Data from each selected study were evaluated individually. All continuous outcomes were calculated by the mean difference or standardized mean difference with 95% confidence interval for each study...
May 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Alessio Molfino, Maria Ida Amabile, Filippo Rossi Fanelli, Maurizio Muscaritoli
INTRODUCTION: Cachexia and sarcopenia are conditions phenotypically characterized by muscle loss and represent a factor of poor prognosis, increasing patients' morbidity and mortality. Cachectic and sarcopenic patients often suffer from low quality of life, presenting lower muscle strength and appetite loss, which makes research on novel treatment strategies to ameliorate clinical response including patient's symptoms, the objective of scientific interest. AREAS COVERED: This article covers recent developments in the area of cachexia and sarcopenia treatment and therapeutic interventions, targeting central nervous system involvement, key inflammatory and muscle-specific metabolic pathways...
October 2016: Expert Opinion on Biological Therapy
Koichi Takayama, Nobuyuki Katakami, Takuma Yokoyama, Shinji Atagi, Kozo Yoshimori, Hiroshi Kagamu, Hiroshi Saito, Yuichi Takiguchi, Keisuke Aoe, Akira Koyama, Naoyuki Komura, Kenji Eguchi
PURPOSE: Cancer cachexia is characterized by decreased body weight (mainly lean body mass [LBM]) and negatively impacts quality of life (QOL) and prognosis. Anamorelin (ONO-7643) is a novel selective ghrelin receptor agonist under development for treating cancer cachexia. METHODS: In this double-blind, exploratory phase 2 trial, we examined the efficacy and safety of anamorelin in Japanese patients (n = 181) with non-small cell lung cancer (NSCLC) and cancer cachexia (≥5 % weight loss within the previous 6 months)...
August 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Jeffrey Crawford
PURPOSE OF REVIEW: This article highlights recent developments in the area of cancer cachexia and therapeutic interventions. RECENT FINDINGS: Therapeutic interventions in cancer cachexia have been guided by clinical studies focused on the central role of muscle and the increased use of CT imaging to measure the impact of skeletal muscle loss on clinical outcomes. At the translational level, a number of different model systems have emphasized the importance of blockade of tumor-induced inflammation and its potential impact on reversing the cachexia phenotype, including FN14, a receptor in the TNF pathway, as well as the parathyroid hormone-related protein...
May 2016: Current Opinion in Clinical Nutrition and Metabolic Care
Jennifer S Temel, Amy P Abernethy, David C Currow, John Friend, Elizabeth M Duus, Ying Yan, Kenneth C Fearon
BACKGROUND: Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia. METHODS: ROMANA 1 and ROMANA 2 were randomised, double-blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 6 months or body-mass index <20 kg/m(2)) were randomly assigned 2:1 to anamorelin 100 mg orally once daily or placebo, with a computer-generated randomisation algorithm stratified by geographical region, cancer treatment status, and weight loss over the previous 6 months...
April 2016: Lancet Oncology
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