Auckland’s Cancer Cachexia evaluating Resistance Training (ACCeRT) main study results

Elaine Sandra Rogers, Rita Sasidharan, Graeme M Sequeira, Matthew R Wood, Stephen P Bird, Justin W L Keogh, Bruce Arroll, Joanna Stewart, Roderick D MacLeod


Background Cancer cachexia is a condition often seen at diagnosis, throughout anticancer treatments and in end stage non-small-cell lung cancer (NSCLC) patients.


Methods Participants with late stage NSCLC 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 cyclo-oxygenase-2 (COX-2) inhibitor celecoxib orally once daily versus same dosing of EPA, celecoxib, plus two sessions per week of progressive resistance training (PRT) and 20 g oral essential amino acids (EAA) high in leucine in a split dose over three days, post each session. Primary endpoint was the acceptability of the above multi-targeted approach. Main secondary endpoints included change in body weight and fat-free mass (FFM), by bioelectric impedance analysis (BIA) and total quadriceps muscle volume by Magnetic Resonance Imaging (MRI) over 20 weeks.


Results 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 PRT sessions and 4·5/5 for EAA within Arm B, all at week 20. Results showed a net gain in BIA FFM 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 MRI 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.


Conclusion NSCLC 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.

Full Text:



Fearon KCH, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489-95.

Muscaritoli M, Bossola M, Aversa Z, Bellantone R, Rossi-Fanelli F. Prevention and treatment of cancer cachexia: New insights into an old problem. Eur J Cancer. 2006;42(1):31-41.

von Haehling S, Anker SD. Treatment of Cachexia: An Overview of Recent Developments. J Am Med Dir Assoc. 2014;15(12):866-72.

Mantovani G, Macciò A, Madeddu C, Gramignano G, Serpe R, Massa E, et al. Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results. Nutrition. 2008;24(4):305-13.

Mantovani G, Macciò A, Madeddu C, Serpe R, Massa E, Dessì M, et al. Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia. Oncologist. 2010;15(2):200-11.

Mantovani G, Macciò A, Madeddu C, Gramignano G, Lusso MR, Serpe R, et al. A Phase II Study with Antioxidants, Both in the Diet and Supplemented, Pharmaconutritional Support, Progestagen, and Anti-Cyclooxygenase-2 Showing Efficacy and Safety in Patients with Cancer-Related Anorexia/Cachexia and Oxidative Stress. Cancer Epidemiol Biomarkers Prev. 2006;15(5):1030-4.

Temel JS, Abernethy AP, Currow DC, Friend J, Duus EM, Yan Y, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol. 2016;17(4):519-31.

Currow D, Temel JS, Abernethy A, Milanowski J, Friend J, Fearon KCH. ROMANA 3: A phase 3 safety extension study of anamorelin in advanced non-small cell lung cancer (NSCLC) patients with cachexia. Ann Oncol. 2017;28(8):1949-56.

Stewart Coats AJ, Ho GF, Prabhash K, von Haehling S, Tilson J, Brown R, et al. Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non‐small cell lung cancer or colorectal cancer: a randomized, double‐blind, placebo‐controlled, international multicentre phase II study (the ACT‐ONE trial). J Cachexia Sarcopenia Muscle. 2016;7(3):355-65.

Wright Traver J, Dillon E. Lichar, Durham William J, Chamberlain Albert, Randolph Kathleen M, Danesi Christopher, et al. A randomized trial of adjunct testosterone for cancer‐related muscle loss in men and women. J Cachexia Sarcopenia Muscle. 2018;9(3):482-96.

Gordon JN, Trebble TM, Ellis RD, Duncan HD, Johns T, Goggin PM. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut. 2005;54(4):540-5.

Fearon KCH, Barber MD, Moses AG, Ahmedzai SH, Taylor GS, Tisdale MJ, et al. Double-Blind, Placebo-Controlled, Randomized Study of Eicosapentaenoic Acid Diester in Patients With Cancer Cachexia. J Clin Oncol. 2006;24(21):3401-7.

Cerchietti LCA, Navigante AH, Castro MA. Effects of Eicosapentaenoic and Docosahexaenoic n-3 Fatty Acids From Fish Oil and Preferential Cox-2 Inhibition on Systemic Syndromes in Patients With Advanced Lung Cancer. Nutr Cancer. 2007;59(1):14-20.

Fearon KCH, von Meyenfeldt MF, Moses AGW, van Geenen R, Roy A, Gouma DJ, et al. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. 2003;52(10):1479-86.

Oldervoll LM, Loge JH, Paltiel H, Asp MB, Vidvei U, Wiken AN, et al. The Effect of a Physical Exercise Program in Palliative Care: A Phase II Study. J Pain Symptom Manage. 2006;31(5):421-30.

Speck RM, Courneya KS, Mâsse LC, Duval S, Schmitz KH. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv. 2010;4(2):87-100.

White CD, Hardy JR. What do palliative care patients and their relatives think about research in palliative care?—a systematic review. Support Care Cancer. 2010;18(8):905-11.

Hudelmaier M, Wirth W, Himmer M, Ring-Dimitriou S, Sänger A, Eckstein F. Effect of exercise intervention on thigh muscle volume and anatomical cross-sectional areas—Quantitative assessment using MRI. Magn Reson Med. 2010;64(6):1713-20.

Boutin RD, Yao L, Canter RJ, Lenchik L. Sarcopenia: Current Concepts and Imaging Implications. AJR Am J Roentgenol. 2015;205(3):W255-W66.

Drummond MJ, Dreyer HC, Fry CS, Glynn EL, Rasmussen BB. Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. Journal of Applied Physiology. 2009;106(4):1374-84.

Madeddu C, Macciò A, Astara G, Massa E, Dessì M, Antoni G, et al. Open phase II study on efficacy and safety of an oral amino acid functional cluster supplementation in cancer cachexia. Med J Nutrition Metab. 2010;3(2):165-72.

Battaglini C, Bottaro M, Dennehy C, Rae L, Shields E, Kirk D, et al. The effects of an individualized exercise intervention on body composition in breast cancer patients undergoing treatment. Sao Paulo Med J. 2007;125:22-8.

Adamsen L, Quist M, Andersen C, Møller T, Herrstedt J, Kronborg D, et al. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ. 2009;339:b3410.

Rogers ES, MacLeod RD, Stewart J, Bird SP, Keogh JWL. A randomised feasibility study of EPA and Cox-2 inhibitor (Celebrex) versus EPA, Cox-2 inhibitor (Celebrex), Resistance Training followed by ingestion of essential amino acids high in leucine in NSCLC cachectic patients - ACCeRT Study. BMC Cancer. 2011;11(1):493.

Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, et al. Cachexia: A new definition. Clin Nutr. 2008;27(6):793-9.

Schulz KF. Subverting randomization in controlled trials. JAMA. 1995;274(18):1456-8.

Solheim TS, Laird BJA, Balstad TR, Stene GB, Bye A, Johns N, et al. A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer. J Cachexia Sarcopenia Muscle. 2017;8(5):778-88.

Ministry of Health. Selected cancers 2012, 2013, 2014 2015 [Available from:

Garon EB, Ciuleanu T-E, Arrieta O, Prabhash K, Syrigos KN, Goksel T, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. The Lancet. 2014;384(9944):665-73.

Greig CA, Johns N, Gray C, MacDonald A, Stephens NA, Skipworth RJE, et al. Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Support Care Cancer. 2014;22(5):1269-75.

Sankaranarayanan R, Kirkwood G, Dibb K, Garratt CJ. Comparison of Atrial Fibrillation in the Young versus That in the Elderly: A Review. Cardiol Res Pract. 2013(Article ID 976976):16 pages.

Farmakis D, Parissis J, Filippatos G. Insights Into Onco-CardiologyAtrial Fibrillation in Cancer. J Am Coll Cardiol. 2014;63(10):945-53.

Courneya KS, Segal RJ, McKenzie DC, Dong H, Gelmon K, Friedenreich CM, et al. Effects of Exercise during Adjuvant Chemotherapy on Breast Cancer Outcomes. Med Sci Sports Exerc. 2014;46(9):1744-51.

Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvão DA, Pinto BM, et al. American College of Sports Medicine Roundtable on Exercise Guidelines for Cancer Survivors. Med Sci Sports Exerc. 2010;42(7):1409-26.

Segal R, Zwaal C, Green E, Tomasone JR, Loblaw A, Petrella T, et al. Exercise for people with cancer: a clinical practice guideline. Curr Oncol. 2017;24(1):40-6.

Stefani L, Galanti G, Klika R. Clinical Implementation of Exercise Guidelines for Cancer Patients: Adaptation of ACSM’s Guidelines to the Italian Model. J Funct Morphol Kinesiol. 2017;2(1):4.

Prado CM, Sawyer MB, Ghosh S, Lieffers JR, Esfandiari N, Antoun S, et al. Central tenet of cancer cachexia therapy: do patients with advanced cancer have exploitable anabolic potential? Am J Clin Nutr. 2013;98(4):1012-9.


  • There are currently no refbacks.