Abstracts of the Cancer Cachexia Conference, Boston, USA, 21–23 September 2012

Abstracts of the Cancer Cachexia Conference, Boston, USA, 21–23 September 2012s of the Cancer Cachexia Conference, Boston, USA, 21–23 September 2012 Published online: 8 November 2012 High-fat diet and obesity exacerbate muscle wasting in experimental cancer cachexia Andrea Bonetto, Chan Ho Lam, Rui Zhan, Felipe E. Pedroso, Leonidas G. Koniaris, Teresa A. Zimmers Department of Cancer Biology, Department of Surgery, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA Obesity and high-fat diet (HFD) are risk factors for multiple types of cancer. Compelling evidence indicates that obesity and diet also play a role after the diagnosis of cancer, influencing treatment, tumor progression, overall well-being and survival. Previously we reported that obesity is associated with increased overall survival in lung cancer patients. Others have shown that HFD was protective in murine MAC16 cachexia. Based on those data and similar obesity risk paradox observations in other diseases, we posited that obesity or HFD might provide increased physiological reserve and slow cachexia in cancer. Here we sought to determine whether diet induced obesity (DIO) or HFD were protective in the Lewis Lung carcinoma mouse model of cancer cachexia. DIO obese and C57Bl/6J lean mice were fed a HFD (60 %kcal from fat), while another lean group was fed normal chow (LFD) (10 %kcal from fat). Mice were inoculated with tumor cells and euthanized 17 and 23 days later. Both obese and lean tumor-bearing mice fed HFD showed increased loss of total body mass, skeletal muscle and fat mass compared with tumor-bearing mice fed LFD. This increased muscle wasting in DIO and HFD mice was associated with greatly reduced plasma insulin and adiponectin levels and increased levels of proinflammatory cytokines IL-6 and LIF versus LFD tumor-bearing controls. In DIO mice, plasma growth factor/cytokine changes corresponded to decreased muscle pAKT and pFOXO3a, and increased pSTAT3 levels, while pSMAD2 and NF-kB levels were unchanged. Taken together, these changes would inhibit anabolism, promote catabolism and drive the inflammatory phenotype, thus contributing to enhanced muscle wasting. In conclusion, our data suggest that both obesity, as a pre-existing condition, and high-fat diet consumption result in worsening of muscle wasting induced by tumor. Furthermore, neither increased body mass nor HFD were protective in experimental cancer cachexia. Effect of Enobosarm on Physical Function in Cancer Patients with < or ≥5 % Weight Loss in a Phase IIb Trial Mitchell S. Steiner; Mary A. Johnston; Michael L. Hancock; James T. Dalton GTx, Inc. Objectives: Although cachexia has been defined as >5 % weight loss, limited data exists on prevention and treatment of muscle wasting prior to becoming cachectic. Cancer-induced muscle wasting begins early resulting in decline in physical function and other detrimental consequences. Methods: We conducted a randomized, double-blind, placebocontrolled study to evaluate enobosarm’s effect on physical function and muscle wasting. Subjects (n0159) received enobosarm or placebo for 16 weeks. Subjects were males >45 y and postmenopausal females, with ≥2 % weight loss in the past 6 months and NSCLC, CRC, CLL, non-Hodgkin’s lymphoma or breast cancer. We report on changes in physical function based on weight loss of </≥5 % in the 6 months prior to randomization. Results: 103 subjects (MITT) had physical function (stair climb) assessed at baseline and week 16 with 24 % losing <5 % weight in previous 6 months. Distribution of weight loss was similar across genders, however subjects with <5 % weight loss were more likely ECOG 0 0 (<5 %: 46.2 %; ≥5 %: 35.8 %). Subjects with ≥5 % weight loss had worse physical function at baseline compared to those with <5 % loss. Significant improvement in physical function was observed in enobosarm subjects regardless of baseline weight loss (<5 %, P0 0.002, ≥5 %, P<0.001) while placebo subjects failed to improve. Conclusions: Enobosarm was well tolerated and showed statistically significant improvement in physical function regardless of baseline weight loss. This provides evidence that enobosarm may play an important role in the management of cancer patients by treating and preventing decline in physical function and muscle wasting before a patient becomes cachectic. Hypothalamic gene expression of appetite regulators in a hyperphagic cancer cachectic mouse model Jvalini T. Dwarkasing, Miriam van Dijk, Francina J. Dijk, Mark V. Boekschoten, A. Visscher, Josep M. Argilès, Alessandro Laviano, Renger F. Witkamp, Klaske van Norren 2 Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, Netherlands, Cancer Research Group, Departament de Bioquímica i Biologia Molecular, University of Barcelona, Barcelona, Spain, Department of Clinical Medicine, Sapienza University, Rome, Italy Appetite regulation is frequently disturbed in cancer patients, often leading to anorexia. It is difficult to understand processes important in J Cachexia Sarcopenia Muscle (2012) 3:281–301 DOI 10.1007/s13539-012-0088-0