Background: Cancer cachexia is a syndrome of weight loss (including muscle and fat), anorexia, and decreased physical function. It has been suggested that the optimal treatment for cachexia should be a multimodal intervention. The primary aim of this study was to examine the feasibility and safety of a multimodal intervention (n‐3 polyunsaturated fatty acid nutritional supplements, exercise, and anti‐inflammatory medication: celecoxib) for cancer cachexia in patients with incurable lung or pancreatic cancer, undergoing chemotherapy.Methods: Patients receiving two cycles of standard chemotherapy were randomized to either the multimodal cachexia intervention or standard care. Primary outcome measures were feasibility assessed by recruitment, attrition, and compliance with intervention (>50% of components in >50% of patients). Key secondary outcomes were change in weight, muscle mass, physical activity, safety, and survival.Results: Three hundred and ninety‐nine were screened resulting in 46 patients recruited (11.5%). Twenty five patients were randomized to the treatment and 21 as controls. Forty‐one completed the study (attrition rate 11%). Compliance to the individual components of the intervention was 76% for celecoxib, 60% for exercise, and 48% for nutritional supplements. As expected from the sample size, there was no statistically significant effect on physical activity or muscle mass. There were no intervention‐related Serious Adverse Events and survival was similar between the groups.Conclusions: A multimodal cachexia intervention is feasible and safe in patients with incurable lung or pancreatic cancer; however, compliance to nutritional supplements was suboptimal. A phase III study is now underway to assess fully the effect of the intervention.

Weight loss limits cancer therapy, quality of life and survival. Common diagnostic criteria and a framework for a classification system for cancer cachexia were recently agreed upon by international consensus. Specific assessment domains (stores, intake, catabolism and function) were proposed. The aim of this study is to validate this diagnostic criteria (two groups: model 1) and examine a four-group (model 2) classification system regarding these domains as well as survival. Data from an international patient sample with advanced cancer (N = 1070) were analysed. In model 1, the diagnostic criteria for cancer cachexia [weight loss/body mass index (BMI)] were used. Model 2 classified patients into four groups 0-III, according to weight loss/BMI as a framework for cachexia stages. The cachexia domains, survival and sociodemographic/medical variables were compared across models. Eight hundred and sixty-one patients were included. Model 1 consisted of 399 cachectic and 462 non-cachectic patients. Cachectic patients had significantly higher levels of inflammation, lower nutritional intake and performance status and shorter survival. In model 2, differences were not consistent; appetite loss did not differ between group III and IV, and performance status not between group 0 and I. Survival was shorter in group II and III compared with other groups. By adding other cachexia domains to the model, survival differences were demonstrated. The diagnostic criteria based on weight loss and BMI distinguish between cachectic and non-cachectic patients concerning all domains (intake, catabolism and function) and is associated with survival. In order to guide cachexia treatment a four-group classification model needs additional domains to discriminate between cachexia stages.

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 increase anabolism, as well as dietary counselling and oral nutritional supplements to promote energy and protein balance. Herein we describe the development of this trial. Trial registration number NCT02330926.

In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g., chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression methods were used to compare these prognostic factors. 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50-2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (p<0.001). Survival at 3 months ranged from 99% (ECOG 0-1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0-1) to 33% (mGPS2, ECOG 3). Performance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone.