{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:29:43Z","timestamp":1791430183269,"version":"4.3.3"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japanese Society for the Promotion of Science","doi-asserted-by":"crossref","award":["23K16438"],"award-info":[{"award-number":["23K16438"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Pharmacological options for refractory cancer pain are limited. This study aimed to investigate the efficacy and safety of the combined use of low-dose methadone and ongoing opioid treatment for uncontrolled cancer pain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a prospective, open-label study. Participants were patients with uncontrolled cancer pain despite dose titration of opioids. Patients received low-dose methadone (starting dose of 5 or 10\u2009mg\/day) combined with another ongoing opioid therapy. The primary outcome was the proportion of responders (defined as \u226533% reduction in average pain intensity on the numerical rating scale [NRS]) on day 15. Pain intensity and adverse events according to the Patient-Reported Outcome Common Terminology Criteria for Adverse Events were evaluated at baseline, on days 8 and 15.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Nineteen patients participated in this study, 11 (57.9%) of whom had neuropathic pain. The mean daily oral morphine equivalent dose before combination was 112.6\u2009mg. The primary outcome occurred in 13 (68.4%) of patients (95% CI, 43.4 to 87.4). The mean average NRS was 5.9 at baseline, which decreased significantly to 4.2 and 3.3 on days 8 and 15 (P\u2009&amp;lt;\u2009.001), respectively. The worst pain intensity on NRS decreased significantly over time. Adverse effects, including nausea, vomiting, constipation, and somnolence, which were new or had worsened from baseline, were reported in 26.3%, 26.3%, 5.3%, and 26.3%, respectively. Delirium was observed in one patient.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Low-dose methadone with ongoing opioid treatment shows potential efficacy in the management of uncontrolled pain with acceptable adverse events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>ClinicalTrials.gov identifier<\/jats:title>\n                  <jats:p>UMIN000038924<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf215","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T14:10:31Z","timestamp":1752502231000},"source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and safety of combining low-dose methadone with ongoing opioid treatment for uncontrolled cancer pain: an open-label single-arm study"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7894-4528","authenticated-orcid":false,"given":"Takaaki","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-6406","authenticated-orcid":false,"given":"Toru","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Psychiatry, Nagoya City University West Medical Center , Nagoya 462-8508,","place":["Japan"]},{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University West Medical Center , Nagoya 462-8508,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4476-892X","authenticated-orcid":false,"given":"Nana","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University West Medical Center , Nagoya 462-8508,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Nursing, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-7452","authenticated-orcid":false,"given":"Yoshihiko","family":"Tasaki","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moeko","family":"Iida","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Ito","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Nursing, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-8400","authenticated-orcid":false,"given":"Megumi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Kubota","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]},{"name":"Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shino","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 467-8601,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"Center for Psycho-oncology and Palliative Care, Nagoya City University Hospital , Nagoya 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