{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:06Z","timestamp":1792789086894,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["UG1CA189823"],"award-info":[{"award-number":["UG1CA189823"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["UG1CA233327"],"award-info":[{"award-number":["UG1CA233327"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180888"],"award-info":[{"award-number":["U10CA180888"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Mu opioid receptors (MORs) in peripheral tissues mediate adverse effects of opioids that impair health-related quality of life (HRQoL) and may stimulate cancer progression via mitogenic signaling. Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation. Safety and efficacy of naloxegol have not been evaluated concurrently with systemic cancer therapy. Methods: We conducted a randomized, double-blind, placebo-controlled trial of naloxegol in patients with advanced lung adenocarcinoma starting first-line systemic therapy. Results: Only 50 patients were enrolled; the trial was terminated early due to slow accrual. Two of the three components of the feasibility primary endpoint were not met (accrual and PRO completion). At 6 months, FACT-L emotional well-being was better with naloxegol (p = 0.0113). There were trends towards better Trial Outcome Index (p = 0.0505) and physical well-being (p = 0.0628) with naloxegol. Bowel function favored naloxegol for constipation (p = 0.0223), rectal pain during defecation (p = 0.0075), and abdominal pain from constipation (p = 0.0113). Adverse event frequency and severity, PRO-CTCAE, urinary hesitancy, pain scores, and progression-free and overall survival were comparable between naloxegol and placebo. Conclusions: Naloxegol appears to be safe and tolerable, with a signal of improved HRQoL and previously unappreciated benefit for emotional well-being, without adverse clinical outcomes. Our findings should be confirmed in larger studies. ClinicalTrials.gov ID: NCT03087708.<\/jats:p>","DOI":"10.3390\/cancers18030373","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T11:14:07Z","timestamp":1769426047000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Naloxegol, an Oral Peripherally Acting Opioid Receptor Antagonist, Administered Concurrently with First-Line Systemic Therapy for Advanced Lung Adenocarcinoma (Alliance A221504): A Feasibility and Safety Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9058-211X","authenticated-orcid":false,"given":"Pankaj","family":"Gupta","sequence":"first","affiliation":[{"name":"VA Long Beach Healthcare System, Long Beach, CA 90822, USA"},{"name":"Department of Medicine, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpna","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Dockter","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Harlos","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Chow","sequence":"additional","affiliation":[{"name":"Alliance Protocol Operations Office, University of Chicago, Chicago, IL 60606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0049-0902","authenticated-orcid":false,"given":"Niveditha","family":"Subbiah","sequence":"additional","affiliation":[{"name":"Alliance Protocol Operations Office, University of Chicago, Chicago, IL 60606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-332X","authenticated-orcid":false,"given":"Kathryn J.","family":"Ruddy","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-4359","authenticated-orcid":false,"given":"Lyudmila","family":"Bazhenova","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby","family":"Terstriep","sequence":"additional","affiliation":[{"name":"Sanford Roger Maris Cancer Center, Fargo, ND 58102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao H.","family":"Huang","sequence":"additional","affiliation":[{"name":"VA Medical Center, Kansas City, MI 64128, USA"},{"name":"University of Kansas Hospital-Westwood Cancer Center, Kansas City, MI 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1599-7494","authenticated-orcid":false,"given":"Robert A.","family":"Kratzke","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everett E.","family":"Vokes","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-5752","authenticated-orcid":false,"given":"Charles L.","family":"Loprinzi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,25]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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