A multi‐targeted treatment approach to cancer cachexia: Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) trial

Abstract

Background Cancer cachexia is a condition often seen at diagnosis, throughout anti‐cancer treatments and in end‐stage non‐small‐cell lung cancer patients. Methods and results Participants with late‐stage non‐small‐cell lung cancer and cachexia (defined as ≥5% weight loss within 12 months) were randomly assigned 1:2 to 2.09 g of eicosapentaenoic acid (EPA) and 300 mg of cyclo‐oxygenase‐2 inhibitor celecoxib orally once daily vs. same dosing of EPA, celecoxib, plus two sessions per week of progressive resistance training and 20 g of oral essential amino acids high in leucine in a split dose over 3 days, after each session. Primary endpoint was the acceptability of the earlier multi‐targeted approach. Main secondary endpoints included change in body weight and fat‐free mass, by bioelectric impedance analysis and total quadriceps muscle volume by magnetic resonance imaging over 20 weeks. Sixty‐nine patients were screened resulting in 20 patients being enrolled. Acceptability scored high, with 4.5/5 (Arm A) and 5/5 (Arm B) for EPA and 5/5 for celecoxib within both arms and 4.8/5 for progressive resistance training sessions and 4.5/5 for essential amino acids within Arm B, all at Week 20. Results showed a net gain in bioelectric impedance analysis fat‐free mass of +1.3 kg, n = 2 (Arm A), compared with +0.7 kg, n = 7 (Arm B) at Week 12, and —1.5 kg, n = 2 (Arm A), compared with —1.7 kg, n = 4 (Arm B) at Week 20. Trends in efficacy in terms of improvement and/or stability in cachexia markers were seen within magnetic resonance imaging muscle volume, albumin, and C‐reactive protein levels within both arms. There were no exercise‐related adverse events, with one possible related adverse event of asymptomatic atrial fibrillation in one participant within Arm A. Conclusions Non‐small‐cell lung cancer cachectic patients are willing to be enrolled onto a multi‐targeted treatment regimen and may benefit from cachexia symptom management even during the late/refractory stage.

Prevalence of Cachexia in Cancer Patients

“…Consistent with this, using a resistance training program, signifcant improvements were obtained in the 6-minute walk test and the sit-stand test, and the lean mass of the lower extremities, as well as knee extensor strength, were increased, realizing that three months of training in patients with cachexia induced by pancreatic cancer led to a delay in the appearance and progression of cachexia in cancer patients, represented by an increase in lean mass compared to the control group [45]. Within the same scope, Rogers et al demonstrated that the application of progressive resistance training to counteract the loss of fat and muscle mass was feasible and highly acceptable for cancer patients [46].…”

Impact of Cancer Cachexia on Cardiac and Skeletal Muscle: Role of Exercise Training

“…A trimodal approach is usually the preferred treatment studied in this population, which includes a combination of exercise, nutritional supplementation, and nonsteroidal anti-inflammatory drugs. The study ACCeRT was a small prospective trial in which 20 adult patients with non-small-cell lung cancer (NSCLC) and refractory cachexia were randomized to receive EPA and celecoxib or EPA, celecoxib, essential amino acids, and RT [ 85 , 86 ]. Interventions in both arms were feasible, and stabilization of body weight and free fat mass could be obtained for some weeks with both approaches [ 85 ].…”

“…The study ACCeRT was a small prospective trial in which 20 adult patients with non-small-cell lung cancer (NSCLC) and refractory cachexia were randomized to receive EPA and celecoxib or EPA, celecoxib, essential amino acids, and RT [ 85 , 86 ]. Interventions in both arms were feasible, and stabilization of body weight and free fat mass could be obtained for some weeks with both approaches [ 85 ]. In Pre-MENAC, a phase II trial with NSCLC and pancreatic cancer patients, celecoxib associated with EPA-enriched supplements and physical exercise (RT and ET) was a safe and viable intervention for pre-cachectic and cachectic individuals [ 87 ].…”

Acceptability, Compliance, and Safety of Non-small Cell Lung Cancer Cachectic Participants Continuing Compassionate Access in the ACCeRT Clinical Study

“…Trends in efficacy, in terms of improvement and/or stability in cachexia markers, were seen within magnetic resonance imaging (MRI) muscle volume, albumin, and C-reactive protein (CRP) levels within both arms. 14 Participants who had completed the ACCeRT main study could continue with medication and/or exercise sessions post end of the main study under compassionate use (CU). Data on the ongoing acceptability, compliance and safety of this multi-targeted regimen in refractory cachectic NSCLC patients will be used to calculate the power and number of participants required for a future phase II study.…”