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Supportive Oncology The Potential of Ghrelin in Cancer Anorexia–Cachexia Jose M Garcia, 1 Aminah Jatoi 2 and Egidio Del Fabbro 3 1. Assistant Professor, Michael E DeBakey Veterans Affairs Medical Center, Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Molecular and Cell Biology, Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, US; 2. Professor, Department of Oncology, Mayo Clinic, Rochester, Minnesota, US; 3. Associate Professor, Director, Palliative Care Program, Division of Hematology, Oncology and Palliative Care, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University, Virginia, US Abstract The cancer anorexia–cachexia syndrome (CACS) is often seen in patients with incurable malignancies and is associated with increased mortality, decreased efficacy of anticancer treatments and poor quality of life. However, there are currently no effective therapies for CACS. Since CACS is a multifactorial syndrome with a complex pathophysiology, therapeutic interventions for CACS might potentially include anabolic agents as well as anti-inflammatory effects. Ghrelin affects numerous key pathways in the regulation of body weight and body composition through increased appetite and growth hormone (GH) secretion. Preliminary clinical data indicate that the administration of ghrelin and ghrelin receptor agonist such as anamorelin have beneficial effects on appetite and body weight in patients with CACS. Anamorelin is currently in phase III clinical trials. Keywords Anamorelin, cancer anorexia–cachexia syndrome, ghrelin Disclosure: Jose M Garcia receives research support and is a consultant for Aeterna Zentaris, Inc. and Helsinn Therapeutics, Inc. Aminah Jatoi has received research funding from Novartis, XBiotech, Aveo and Enterahealth. She has served as a consultant to Helsinn. Egidio Del Fabbro has been a consultant for and on the advisory board for Helsinn Therapeutics. Acknowledgements: This material is also based upon work supported with resources and the use of facilities at the Houston Veterans Affairs. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. Editorial assistance was provided by Katrina Mountfort at Touch Medical Media. Received: 2 September 2013 Accepted: 5 November 2013 Citation: European Oncology & Haematology, 2013;9(2):77–83 Correspondence: Jose M Garcia, Assistant Professor, Michael E DeBakey Veterans Affairs Medical Center, Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Molecular and Cell Biology, Huffington Center on Aging, Baylor College of Medicine, 2002 Holcombe Blvd, Houston, Texas, 77030, US. E: Support: The publication of this article was supported by Helsinn Therapeutics. The views and opinions expressed are those of the authors and not necessarily those of Helsinn Therapeutics. Cachexia is a complex metabolic disorder that results in progressive weight loss, muscle and adipose tissue wasting and inflammation and is frequently observed in patients with incurable malignancies. 1 Weight loss in cancer patients results from reduction in adipose tissue and skeletal mass. Anorexia is defined as the loss of desire to eat. Although anorexia frequently accompanies cachexia, there does not appear to be a cause–effect relationship between the two. Anorexia occurs in almost half of patients with cancer, 2,3 and can be present even in patients not receiving chemotherapy. 4 Although our understanding of cachexia has increased over the last decade, lack of consensus on its definition, diagnostic criteria and classification have impaired the development of therapeutic interventions. In 2011, an international consensus panel defined cancer anorexia–cachexia syndrome (CACS) as a multifactorial group of signs and symptoms defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) and by the fact that these changes are not able to be fully reversed by conventional nutritional support. The result of this detrimental process is functional impairment and early demise. 5 The incidence of CACS depends on the tumour type and ranges from 16  % to over 50  % of patients. 6,7 The degree of severity also varies, with loss of more than 10  % body weight in 15  % of patients. 8 The highest incidence occurs in patients with solid tumours, in particular © To u ch MEd ica l MEdia 2013 pancreatic and gastric cancers, where weight loss is seen in over 80  % of patients. The lowest incidence is seen in patients with non- Hodgkin lymphoma, breast cancer, acute non-lymphocytic leukaemia and sarcomas. 9 More than 50 % of patients with cancer die with CACS being present. 7 It should be noted, however, that the percentage above are heavily influenced by the scope of practice or clinical setting from which they have been derived, and, in this review, we point out that CACS is by definition observed in patients with advanced, incurable malignancies. CACS is associated with poor QoL, 1,10–13 poor physical function, 10,12 decreased response to therapy, 14,15 decreased tolerance to therapy 1,5,16 and poor prognosis. 9,10,17,18 A meta-analysis of 30 randomised controlled trials from the European Organisation for Research and Treatment of Cancer (EORTC) found a significant correlation between poor appetite and poor prognosis. 19 The predictive value of CACS is independent of disease stage and performance status. Diagnostic criteria for CACS were recently established by a consensus group and are summarised in Table 1. The same group concluded that cachexia progresses through three stages. Precachexia involves a weight loss ≤5 %, anorexia and metabolic change. Cachexia comprises a weight loss >5 % or body mass index (BMI) <20 and weight loss >2 % 77