{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:36:16Z","timestamp":1791938176055,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer cachexia is a major cause of morbidity and mortality with no widely approved treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The ACT\u2010ONE trial is a randomized, double\u2010blind, parallel group, placebo\u2010controlled, phase II multicentre trial in patients (25\u201080\u2009years) with stages III or IV colorectal cancer or non\u2010small cell lung cancer\u2010related cachexia that tested two doses of espindolol (a novel non\u2010selective \u03b2 blocker with central 5\u2010HT1a and partial \u03b22 receptor agonist effects). The primary endpoint was the difference in the rate of weight change over 16\u2009weeks (linear mixed\u2010effect model for repeated measures) between high\u2010dose espindolol and placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighty\u2010seven patients were randomized centrally in blocks in a ratio 3:2:1 [42 high dose, 10\u2009mg twice daily (bd):31 placebo:14 low dose, 2.5\u2009mg bd]. High\u2010dose espindolol produced a statistically and clinically significant weight gain (+0.54\u2009kg\/4\u2009weeks, 95% CI 0.38\u20130.70) compared with a weight loss on placebo (\u22120.21\u2009kg\/4\u2009weeks, 95% CI \u20100.37\u20130.05); <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001. High\u2010dose espindolol produced a statistically significant increase in lean body mass, whilst changes in fat mass were neutral. Hand grip strength significantly (high dose \u22121.15\u2009\u00b1\u20090.7\u2009kg, placebo \u22123.51\u2009\u00b1\u20090.8\u2009kg change per 4\u2009weeks; <jats:italic>P<\/jats:italic>\u2009=\u20090.0134), stair climbing power, and 6\u2010min walk test non\u2010significantly were all directionally in favour of high\u2010dose espindolol. There were no clinically significant differences in safety signals or survival between treatment groups, although a numerical excess of dyspnoea was seen with high\u2010dose espindolol (19.1%) compared with placebo (3.2%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This positive trial showed that espindolol 10\u2009mg bd significantly reversed weight loss, improved fat free mass, and maintained fat mass in advanced colorectal cancer and non\u2010small cell lung cancer\u2010related cachexia. This was associated with a significant improvement in handgrip strength, supporting the further investigation of 10\u2009mg bd espindolol for the treatment of cancer cachexia. Although not powered to look at dose response, most treatment effects for low dose lay between high dose and placebo, suggesting that there may be a dose response in the effects of espindolol.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12126","type":"journal-article","created":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T11:26:01Z","timestamp":1467372361000},"page":"355-365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":162,"title":["Espindolol for the treatment and prevention of cachexia in patients with stage III\/IV non\u2010small cell lung cancer or colorectal cancer: a randomized, double\u2010blind, placebo\u2010controlled, international multicentre phase II study (the ACT\u2010ONE trial)"],"prefix":"10.1002","volume":"7","author":[{"given":"Andrew J.","family":"Stewart Coats","sequence":"first","affiliation":[{"name":"Monash University  Melbourne Australia"},{"name":"Warwick University  Coventry UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwo Fuang","family":"Ho","sequence":"additional","affiliation":[{"name":"Universiti Malaya Medical  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Prabhash","sequence":"additional","affiliation":[{"name":"Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"von Haehling","sequence":"additional","affiliation":[{"name":"Division of Innovative Clinical Trials, Department of Cardiology University Medical Center G\u00f6ttingen (UMG)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Tilson","sequence":"additional","affiliation":[{"name":"PsiOxus Therapeutics Limited  Abingdon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Brown","sequence":"additional","affiliation":[{"name":"PsiOxus Therapeutics Limited  Abingdon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Beadle","sequence":"additional","affiliation":[{"name":"PsiOxus Therapeutics Limited  Abingdon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Division of Innovative Clinical Trials, Department of Cardiology University Medical Center G\u00f6ttingen (UMG)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for and on behalf of the ACT\u2010ONE study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2008.06.013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3829"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198304213081606"},{"key":"e_1_2_10_5_1","first-page":"80","article-title":"\u03b2\u2010adrenergic agonists: substances with anabolic effect in animals for meat production","volume":"14","author":"Pleadin J","year":"2012","journal-title":"MESO: prvi hrvatski \u010dasopis o mesu"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21723"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543781003724690"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-013-0125-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"S501","DOI":"10.14309\/00000434-200709002-01045","article-title":"A randomised, controlled, double\u2010blind trial of s\u2010pindolol in irritable bowel syndrome (IBS)","volume":"102","author":"Quigley EM","year":"2007","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-011-0046-2"},{"key":"e_1_2_10_11_1","unstructured":"Bassey Hand grip strength test NIH 1990."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2007.02.004"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/49.2.M85"},{"key":"e_1_2_10_14_1","first-page":"783","article-title":"The six\u2010minute walk test","volume":"48","author":"Enright PL","year":"2003","journal-title":"Respir Care"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-198212000-00014"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70055-X"},{"key":"e_1_2_10_17_1","unstructured":"CrawfordJC JohnstonMA HancockML SmallSG TaylorRP DaltonJP 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. 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