Cancer cachexia: rationale for the MENAC (Multimodal—Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial

Abstract

Cancer cachexia is a multifactorial syndrome characterized by an on-going 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 randomized controlled trial of a multimodal cachexia intervention is underway.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 Antiinflammatory Drugs (NSAID) and eicosapentaenoic acid (EPA) 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.

Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia

“…Additionally, physical activity seems to be an important element for the treatment of cancer cachexia . Exercise training programs (such as strength and/or aerobic training) demonstrated to have a very clear anti‐inflammatory effect, decreasing pro‐inflammatory cytokines and increasing anti‐inflammatory cytokines .…”

The evolution of body composition in oncology—epidemiology, clinical trials, and the future of patient care: facts and numbers

“…protein), and pharmacotherapy may be necessary to provide a sufficient stimulus to prevent or slow the cascade of tissue wasting ( Figure 2). 79 Studies to date have focused on the importance of muscle; however, greater attention to the prognostic effects of excess adiposity and the development of interventions with the potential to simultaneously increase muscle and reduce adiposity may be of critical importance. Early intervention to prevent the deterioration of body composition may be more effective than efforts to improve body composition in patients with established cachexia.…”

“…An example of a multimodal intervention that is being tested within an ongoing phase III trial includes non-steroidal anti-inflammatory medication, eicosapentaenoic acid, resistance and aerobic exercise, and dietary counselling with oral nutritional supplements to prevent weight loss and the deterioration of body composition in patients with advanced or metastatic cancer. 79 Studies to date have focused on the importance of muscle; however, greater attention to the prognostic effects of excess adiposity and the development of interventions with the potential to simultaneously increase muscle and reduce adiposity may be of critical importance. Continued efforts to investigate the efficacy of multimodal interventions are urgently needed to advance this area.…”

High‐intensity interval training slows down tumor progression in mice bearing Lewis lung carcinoma

“…Most of advanced oncologic patients display skeletal muscle wasting associated with functional impairment, and lung cancer patients with cachexia display shorter survival than non‐cachectic ones [35]. In this context, the lack of therapies for cancer cachexia is still evident [36]. By using LLC tumor‐bearing mice, Penna et al (2011) have previously demonstrated that moderate‐intensity aerobic exercise training protocol associated with EPA administration mitigated muscle wasting [20].…”