{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:20:07Z","timestamp":1784866807399,"version":"3.55.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"UMIN Clinical Trials Registry under registration no","award":["UMIN000015579"],"award-info":[{"award-number":["UMIN000015579"]}]},{"name":"Japan Agency for Medical Research and Development (Innovative Clinical Cancer Research:","award":["16ck0106060h0003"],"award-info":[{"award-number":["16ck0106060h0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We hypothesized that the high-dose opioid requirement in patients carrying the rs4680-GG variant in the COMT gene encoding catechol-O-methyltransferase would be greater for patients taking morphine than for those taking oxycodone, thus providing a much-needed biomarker to inform opioid selection for cancer pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, multicenter, open-label trial was conducted at a Japanese hospital\u2019s palliative care service. Patients with cancer pain treated with regular doses of nonsteroidal anti-inflammatory drugs or acetaminophen were enrolled and randomized (1:1) into morphine (group M) and oxycodone (group O) groups. The minimum standard dose of immediate-release (IR) oral opioids was repeatedly administered by palliative care physicians to achieve pain-reduction goals (Pain reduction\u2005\u2265\u200533% from baseline and up to\u2005\u2264\u20053 on a numerical rating scale). The primary endpoint was the proportion of subjects requiring high-dose opioids on day 0 with the GG genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 140 participants who developed cancer-related pain among 378 subjects registered and pre-screened for the genotype, 139 were evaluated in the current study. Among patients carrying a COMT rs4680-GG genotype, 48.3% required high-dose opioids in group M, compared with the 20.0% in group O (95% CI, 3.7%-50.8%; P\u2005=\u2005.029). Of those with the non-GG genotype, 41.5% treated with morphine and 23.1% with oxycodone required high-dose opioids (95% CI, 3.3%-38.3%; P\u2005=\u20050.098).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using the COMT rs4680 genotype alone is not recommended for selecting between morphine and oxycodone for pain relief.<\/jats:p><\/jats:sec>","DOI":"10.1093\/oncolo\/oyac233","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T12:32:50Z","timestamp":1669379570000},"page":"278-e166","source":"Crossref","is-referenced-by-count":7,"title":["Morphine Versus Oxycodone for Cancer Pain Using a Catechol-O-methyltransferase Genotype Biomarker: A Multicenter, Randomized, Open-Label, Phase III Clinical Trial (RELIEF Study)"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7276-1971","authenticated-orcid":false,"given":"Hiromichi","family":"Matsuoka","sequence":"first","affiliation":[{"name":"Department of Psychosomatic Medicine, Kindai University Faculty of Medicine , Osaka , Japan"},{"name":"Palliative Care Center, Kindai Hospital , Osaka , Japan"},{"name":"Palliative Care Team, National Cancer Center , Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6260-6943","authenticated-orcid":false,"given":"Junji","family":"Tsurutani","sequence":"additional","affiliation":[{"name":"Advanced Cancer Translational Research Institute, Showa University , Tokyo , Japan"},{"name":"Department of Medical Oncology, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Biostatics, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Genome Biology, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohiro","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, Kindai University Faculty of Medicine , Osaka , Japan"},{"name":"Palliative Care Center, Kindai Hospital , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Palliative Care Center, Kindai Hospital , Osaka , Japan"},{"name":"Department of Medical Oncology, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Nakura","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Makimura","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Ohtake","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, Kindai University Faculty of Medicine , Osaka , Japan"},{"name":"Department of Internal Medicine, Sakai City Medical Center , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Okuno","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kindai University Faculty of Medicine , Osaka , 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kindai University Faculty of Medicine , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"issue":"3","key":"2023041012083286000_","first-page":"1423","article-title":"Pain polymorphisms and opioids: an evidence-based review","volume":"19","author":"Vieira","year":"2019","journal-title":"Mol Med Rep"},{"issue":"9","key":"2023041012083286000_","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/phar.1986","article-title":"Review of opioid pharmacogenetics and considerations for pain management","volume":"37","author":"Owusu 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