{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:17:31Z","timestamp":1785885451628,"version":"3.56.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,8,28]],"date-time":"2017-08-28T00:00:00Z","timestamp":1503878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pain Practice"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pain is still a burden for many patients with cancer. A recent trial showed the superiority of methadone over fentanyl in neuropathic pain, and we expect that this finding could influence the number of patients treated with methadone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a randomized controlled noninferiority trial in patients with nociceptive pain. Eighty\u2010two strong\u2010opioid\u2010na\u00efve patients with head and neck cancer with substantial pain (pain numeric rating scale [NRS] score \u2265\u00a04) due to radiation therapy were included. Forty\u2010two patients were treated with methadone, and 40 with fentanyl. Patients were evaluated at 1, 3, and 5\u00a0weeks. The primary outcomes were reduction in average pain and clinical success (50% pain decrease). We set the predefined noninferiority margin at 1 on the NRS and 10% clinical success. Secondary outcomes were pain interference, global perceived effect (GPE), side effects, and opioid escalation index.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Noninferiority was shown for decrease in NRS for maximum and mean pain scores at 1 and 3\u00a0weeks. Noninferiority was shown for clinical success at 1\u00a0week only. The opioid escalation index was lower in the methadone group at 3 and 5\u00a0weeks as compared to fentanyl (1.44 vs. 1.99, P\u00a0=\u00a00.004; and 1.50 vs. 2.32, P\u00a0=\u00a00.013). The pain interference in the methadone group was significantly decreased at 3\u00a0weeks only. GPE and side effects were not different.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first study to show noninferiority of methadone compared to fentanyl at 1 and 3\u00a0weeks in the treatment of radiation\u2010induced nociceptive pain in patients with head and neck cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/papr.12609","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T09:03:28Z","timestamp":1499677408000},"page":"331-340","source":"Crossref","is-referenced-by-count":18,"title":["Methadone versus Fentanyl in Patients with Radiation\u2010Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial"],"prefix":"10.1111","volume":"18","author":[{"given":"Johan","family":"Haumann","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Management Maastricht University Medical Centre University Pain Centre Maastricht Maastricht The Netherlands"},{"name":"Department of Anesthesiology and Pain Management Onze Lieve Vrouwe Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander M.J.","family":"van Kuijk","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Management Maastricht University Medical Centre University Pain Centre Maastricht Maastricht The Netherlands"},{"name":"Department of Clinical Epidemiology and Medical Technology Assessment Maastricht University Medical Centre Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 W.","family":"Geurts","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Management Maastricht University Medical Centre University Pain Centre Maastricht Maastricht The Netherlands"},{"name":"Department of Anesthesiology and Pain Medicine Rijnstate Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.P.","family":"Hoebers","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology GROW School for Oncology and Developmental Biology Maastricht University Medical Centre Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head &amp; Neck Surgery GROW School for Oncology and Developmental Biology Maastricht University Medical Centre Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elbert A.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Management Maastricht University Medical Centre University Pain Centre Maastricht Maastricht The Netherlands"},{"name":"Department of Translational Neuroscience School of Mental Health and Neuroscience Maastricht University Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke H.J.","family":"van den Beuken\u2010van Everdingen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Management Maastricht University Medical Centre University Pain Centre Maastricht Maastricht The Netherlands"},{"name":"Centre of Expertise for Palliative Care Maastricht University Medical Centre Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.36076\/ppj.2013\/16\/379","article-title":"Pain and its interference with daily activities in medical oncology outpatients","volume":"16","author":"Boveldt N","year":"2013","journal-title":"Pain Physician"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2015.12.340"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00324-4"},{"issue":"4","key":"e_1_2_8_5_1","first-page":"CD003971","article-title":"Methadone for cancer pain","author":"Nicholson AB","year":"2007","journal-title":"Cochrane Database Syst Rev"},{"issue":"10","key":"e_1_2_8_6_1","first-page":"CD010270","article-title":"Transdermal fentanyl for cancer pain","author":"Hadley G","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"e_1_2_8_7_1","first-page":"CD009596","article-title":"Buprenorphine for treating cancer pain","author":"Schmidt\u2010Hansen M","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"issue":"2","key":"e_1_2_8_8_1","first-page":"CD003870","article-title":"Oxycodone for cancer\u2010related pain","author":"Schmidt\u2010Hansen M","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079904X2114"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-29-67"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/jpm.2007.0200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.06.025"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-3924(99)00064-0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(96)03147-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(95)00156-5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00349-9"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291796004382"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1983.tb09716.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8510(90)90421-9"},{"issue":"11","key":"e_1_2_8_20_1","first-page":"CD008025","article-title":"Methadone for chronic non\u2010cancer pain in adults","author":"Haroutiunian S","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2008.01.013"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12630-015-0551-4"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2012.01334.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/15360288.2014.938883"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.593"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.06.047"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-009-0649-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000867"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2008.01597.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5055\/jom.2013.0167","article-title":"Prolonged QT interval by methadone: relevance for daily practice? 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