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

Authors

  • Elaine S Rogers Department of General Practice and Primary Health Care, University of Auckland, Auckland, 1142 New Zealand and Department of Medical Oncology, Auckland City Hospital, Auckland, 1023 New Zealand.
  • Rita Sasidharan Department of Medical Oncology, Auckland City Hospital, Auckland, 1023 New Zealand.
  • Graeme M Sequeira School of Sport, Manukau Institute of Technology, Auckland, 2241 New Zealand.
  • Matthew R Wood Sports Performance Research Institute New Zealand (SPRINZ), Auckland University of Technology, Auckland, 1010 New Zealand.
  • Stephen P Bird Department of Medical and Exercise Science, University of Wollongong, New South Wales, 2522 Australia.
  • Justin W L Keogh Faculty of Health Sciences and Medicine, Bond University, Gold Coast, 4226 Australia.
  • Bruce Arroll Department of General Practice and Primary Health Care, University of Auckland, Auckland, 1142 New Zealand.
  • Joanna Stewart Department of Epidemiology and Biostatistics, University of Auckland, Auckland, 1142 New Zealand.
  • Roderick D MacLeod Northern Clinical School, University of Sydney, Sydney, New South Wales, 2065 Australia.

DOI:

https://doi.org/10.31584/jhsmr.2021842

Keywords:

Refractory cancer cachexia, Resistance Training, NSCLC cachectic patients, multi-targeted treatment

Abstract

Objective: Cancer cachexia is defined as: a ‘multifactorial syndrome’, and it has been suggested that a multitargeted approach is required in its management. High prevalence is seen within non-small cell lung cancer, and patients may continue to experience cachexia post end of anti-cancer treatment, and in the late/end stage.

Material and Methods: Participants who had completed week 20/End of Trial visit in the main Auckland’s Cancer Cachexia evaluating Resistance Training (ACCeRT) study were invited to continue with treatment under compassionate use. Participants could continue with 2.09 g of eicosapentaenoic acid (EPA), 300 mg COX-2 inhibitor (celecoxib), once daily; 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. Data was collected on the acceptability, compliance and adherence to medication/PRT sessions. Secondary endpoints included: change in body weight and fat free mass handgrip and leg strength, the Functional Assessment of Anorexia/Cachexia Therapy, Multidimensional Fatigue Symptom Inventory-Short Form, World Health Organization Quality of Life — BREF, Glasgow prognostic score, and pro-inflammatory cytokines.

Results: All six participants, who completed the main ACCeRT study, opted to continue with compassionate use. Acceptability remained high, with overall compliance to last study/PRT visit of 81.0% for EPA, 98.8% for celecoxib, 78.9% for PRT and 77.2% for EAA. Participants continued to lose body weight and Fat-Free Mass, along with reduced albumin and increased C-Reactive protein levels. Mean time on compassionate study treatment was 78 days, and with a mean overall survival of 257 days (140 + 117).

Conclusion: Non-small cell lung cancer (NSCLC) cachectic patients are willing to be enrolled onto a multi-targeted treatment regimen, and may benefit from cachexia symptom management even during their late/refractory stage.

References

Vagnildhaug OM, Balstad TR, Almberg SS, Brunelli C, Knudsen AK, Kaasa S et al. A cross-sectional study examining the prevalence of cachexia and areas of unmet need in patients with cancer. Support Care Cancer 2018;26:1871- 80.

Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 1980;69:491-7.

Andreyev HJN, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer 1998;34:503-9.

McQuade JL, Daniel CR, Hess KR, Mak C, Wang DY, Rai RR, et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol 2018;19:310-22.

Lennon H, Sperrin M, Badrick E, Renehan AG. The obesity paradox in cancer: a review. Curr Oncol Rep 2016;18:1-8.

Greenlee H, Unger JM, LeBlanc M, Ramsey S, Hershman DL. Association between body mass index and vancer durvival in a pooled analysis of 22 clinical trials. Cancer Epidemiol Biomarkers Prev 2017;26:21-9.

Coss CC, Clinton SK, Phelps MA. Cachectic Cancer Patients: Immune to Checkpoint Inhibitor Therapy?. Clin Cancer Res 2018;24:5787-9.

Turner DC, Kondic AG, Anderson KM, Robinson AG, Garon EB, Riess JW, et al. Pembrolizumab exposure–response assessments challenged by association of cancer cachexia and catabolic clearance. Clin Cancer Res 2018;24:5841-9

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: 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;42:31-41.

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: 778-88.

Wakabayashi H, Arai H, Inui A. The regulatory approval of anamorelin for treatment of cachexia in patients with non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer in Japan: facts and numbers. J Cachexia Sarcopenia Muscle 2021;12:14-6.

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;11:493.

Rogers ES, Sasidharan R, Sequeira GM, Wood MR, Bird SP, Keogh JWL, et al. A multi-targeted treatment approach to cancer cachexia: Auckland’s Cancer Cachexia evaluating Resistance Training (ACCeRT) trial. JCSM Rapid Commun 2020;3:11-24.

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;54:540-5.

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;24:3401-7.

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;18:519-31.

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;28:1949-56.

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;7:355-65.

Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol 2013;14:335- 45.

Downloads

Published

2021-10-05

How to Cite

1.
Rogers ES, Sasidharan R, Sequeira GM, Wood MR, Bird SP, Keogh JWL, Arroll B, Stewart J, MacLeod RD. Acceptability, Compliance, and Safety of Non-small Cell Lung Cancer Cachectic Participants Continuing Compassionate Access in the ACCeRT Clinical Study. J Health Sci Med Res [Internet]. 2021 Oct. 5 [cited 2024 Dec. 23];40(3):335-47. Available from: https://he01.tci-thaijo.org/index.php/jhsmr/article/view/255393

Issue

VOL 40, NO 3(2022): May-Jun

Section

Original Article

License

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Crossref
Scopus
Google Scholar
Europe PMC