The ACCeRT Study - Auckland’s Cancer Cachexia evaluating Resistance Training Study: A randomised feasibility study of EPA and Cox-2 inhibitor (Celecoxib) versus EPA, Cox-2 inhibitor (Celecoxib), Progressive Resistance Training followed by ingestion of essential amino acids high in leucine in NSCLC cachectic participants

Abstract

Background: Cancer cachexia is a common problem in Non-Small Cell Lung Cancer (NSCLC). In cancer cachexia there is a significant loss of adipose tissue and skeletal muscle mass. There is a need to utilise a multi-targeted approach to decrease the inflammation process and stimulate the skeletal anabolic pathways with the use of progressive resistance training (PRT) and Essential Amino Acids (EAA). Methods: ACCeRT is a randomised controlled feasibility, open-label study, investigating the acceptability, trends in efficacy and safety of a multi-targeted approach in end-stage NSCLC cachectic patients, over 20 weeks. Participants were randomised in a 1:2 ratio to Eicosapentaenoic acid (EPA) and celecoxib (Arm A), versus EPA, celecoxib, two sessions of supervised PRT per week, followed by 20g EAA over 3 days (Arm B). Results: Twenty participants enrolled in the study, seven in Arm A, and 13 in Arm B. The mean age at entry was 68.2 years and 7.95% weight loss. Acceptability scored high on an acceptability questionnaire, with 100% for EPA and celecoxib within both Arms, and 100% for PRT sessions and EAA within Arm B. Compliance was also high with 99.6% (Arm A) and 86.8% (Arm B) for EPA, 60.7% (Arm A) and 100% (Arm B) for celecoxib, 94.4% for PRT sessions and 76.5% for EAA, all at week 20. Results showed a net gain in BIA FFM of +1.3kg, n=2 (Arm A), compared with +0.7kg, n=7 (Arm B) at week 12, and -1.5kg, n=2 (Arm A), compared with ˗1.7kg, n=4 (Arm B) at week 20. Trends in efficacy in terms of improvement and stability in cachexia markers were seen within BIA FFM and weight, IL-6 and TNF-α levels, albumin and CRP levels, MRI, FAACT-PWB and MFSI-SF-Total scores within both Arms. There were no exercise-related adverse events, with one possible related AE of asymptomatic atrial fibrillation in one participant within Arm A. Conclusion: The above trends in efficacy in a number of cachexia markers within both Arms, and the minimal toxicity support further evaluation of this regimen within a larger phase II study. These data can serve as a baseline for future refractory cachexia studies.