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)

Journal of Cachexia, Sarcopenia and Muscle

Volumn , Issue , 2016, Pages 355-365

  Stewart Coats, Andrew J ^a,b   Ho, Gwo Fuang ^c   Prabhash, Kumar ^d   von Haehling, Stephan ^e   Tilson, Julia ^f   Brown, Richard ^f   Beadle, John ^f   Anker, Stefan D ^e  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF WARWICK   (United Kingdom)

^c UNIVERSITY OF MALAYA   (Malaysia)

^d TATA MEMORIAL HOSPITAL   (India)

^e UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^f PSIOXUS THERAPEUTICS LTD   (United Kingdom)

Author keywords

Cachexia; Cancer; Espindolol; Randomized controlled study

Indexed keywords

ANABOLIC AGENT; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; CARBOPLATIN; CISPLATIN; ESPINDOLOL; FLUOROURACIL; IRINOTECAN; OXALIPLATIN; PLACEBO; PROTECTIVE AGENT; SEROTONIN 1A AGONIST; UNCLASSIFIED DRUG;

ADULT; AGED; ANEMIA; ARTICLE; BODY FAT; CACHEXIA; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER SURVIVAL; COLORECTAL CANCER; COMORBIDITY; CONTROLLED STUDY; COUGHING; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG MEGADOSE; DRUG SAFETY; DUAL ENERGY X RAY ABSORPTIOMETRY; DYSPNEA; FAT MASS; FEMALE; FOLLOW UP; HUMAN; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NON SMALL CELL LUNG CANCER; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROPHYLAXIS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; WEIGHT CHANGE; WEIGHT REDUCTION;

EID: 84978864205     PISSN: 21905991     EISSN: 21906009     Source Type: Journal    
DOI: 10.1002/jcsm.12126     Document Type: Article

References (28)

1. Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, et al. Cachexia: a new definition. Clin Nutr 2008;27:793–799.
2. Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer 2014;14:754–762.
3. Frishman WH. Pindolol: a new β-adrenoceptor antagonists with partial agonist activity. N Engl J Med 1983;308:940–944.
4. Pleadin J, Vulić A, Perši N. β-adrenergic agonists: substances with anabolic effect in animals for meat production. MESO: prvi hrvatski časopis o mesu 2012;14:80–87.
5. Palm D, Lang K, Niggemann B, Drell TL, Kai Masur K, Zaenker KS, et al. The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by β-blockers. Int J Cancer 2006;118:2744–2749.
6. Kung T, Springer J, Doehner W, Anker SD, von Haehling S. Novel treatment approaches to cachexia and sarcopenia: highlights from the 5th Cachexia Conference. Expert Opin Investig Drugs 2010;4:579–585.
7. Pötsch MS, Tschirner A, Palus S, von Haehling S, Doehner W, Beadle J, et al. The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats. J Cachexia Sarcopenia Muscle 2014;5:149–158.
8. Quigley EM, Devane J, Young D, Butler J. A randomised, controlled, double-blind trial of s-pindolol in irritable bowel syndrome (IBS). Am J Gastroenterol 2007;102:S501.
9. Stewart Coats AJ, Srinivasan V, Surendran J, Chiramana H, Vangipuram SR, Bhatt NN, et al. The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: study design. J Cachexia Sarcopenia Muscle 2011;2:201–207.
10. Bassey Hand grip strength test NIH, 1990.
11. Bean JF, Kiely DK, LaRose S, Alian J, Frontera WR. Is stair climb power a clinically relevant measure of leg power impairments in at-risk older adults? Arch Phys Med Rehabil 2007;88:604–649.
12. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:M85–M94.
13. Enright PL. The six-minute walk test. Respir Care 2003;48:783–785.
14. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–655.
15. Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, et al. Effects of enobosgroup on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol 2013;14:335–345.
16. Crawford JC, Johnston MA, Hancock ML, Small SG, Taylor RP, Dalton JP, et al. Enobosarm, a selective androgen receptor modulator (SARM) increases lean body mass (LBM) in advanced NSCLC patients; updated results of two pivotal, international Phase 3 trials. Presented at the MASCC/ISOO International Symposium on Supportive Care in Cancer. Miami, FL. June 26-28, 2014. Abstract MASCC-0546. (Abstract)
17. Garcia JM, Friend J, Allen S. Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomised, double-blind, crossover, pilot study. Support Care Cancer 2013;21:129–137.
18. Garcia JM, Boccia RV, Graham CD, Yan Y, Duus EM, Allen S, et al. Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Lancet Oncol 2015;16:108–116.
19. 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. pii: S1470-2045(15)00558-6.;doi:10.1016/S1470-2045(15)00558-6.
20. Kraft M, Kraft K, Gärtner S, Mayerle J, Simon P, Weber E, et al. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)—a randomised multicentre trial. Nutr J 2012;11:52.
21. Yeh KY, Wang HM, Chang JW, Huang JS, Lai CH, Lan YJ, et al. Omega-3 fatty acid-, micronutrient-, and probiotic-enriched nutrition helps body weight stabilization in head and neck cancer cachexia. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:41–48.
22. Del Fabbro E, Dev R, Hui D, Palmer L, Bruera E. Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: a double-blind placebo-controlled trial. J Clin Oncol 2013;31:1271–1276.
23. Wiedenmann B, Malfertheiner P, Friess H, Ritch P, Arseneau J, Mantovani G, et al. A multicenter, phase II study of infliximab plus gemcitabine in pancreatic cancer cachexia. J Support Oncol 2008;6:18–25.
24. Wu C, Fernandez SA, Criswell T, Chidiac TA, Guttridge D, Villalona-Calero M, et al. Disrupting cytokine signaling in pancreatic cancer: a phase I/II study of etanercept in combination with gemcitabine in patients with advanced disease. Pancreas 2013;42:813–818.
25. Yennurajalingam S, Willey JS, Palmer JL, Allo J, Del Fabbro E, Cohen EN, et al. The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: results of a double-blind placebo-controlled randomised study. J Palliat Med 2012;15:1059–1064.
26. http://www.biotech-intelligence.com/html/html/2a462148882a297c8eafbeafbaeff7ff.html.
27. Lainscak M, Keber I, Anker SD. Body composition changes in patients with systolic heart failure treated with beta-blockers: a pilot study. Int J Cardiol 2006;106:319–322.
28. von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle. J Cachexia Sarcopenia Muscle 2015;4:315–316.