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Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)

BACKGROUND: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is r...

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Autores principales: Matsuoka, Hiromichi, Tsurutani, Junji, Chiba, Yasutaka, Fujita, Yoshihiko, Terashima, Masato, Yoshida, Takeshi, Sakai, Kiyohiro, Otake, Yoichi, Koyama, Atsuko, Nishio, Kazuto, Nakagawa, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639590/
https://www.ncbi.nlm.nih.gov/pubmed/28985716
http://dx.doi.org/10.1186/s12885-017-3664-z
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author Matsuoka, Hiromichi
Tsurutani, Junji
Chiba, Yasutaka
Fujita, Yoshihiko
Terashima, Masato
Yoshida, Takeshi
Sakai, Kiyohiro
Otake, Yoichi
Koyama, Atsuko
Nishio, Kazuto
Nakagawa, Kazuhiko
author_facet Matsuoka, Hiromichi
Tsurutani, Junji
Chiba, Yasutaka
Fujita, Yoshihiko
Terashima, Masato
Yoshida, Takeshi
Sakai, Kiyohiro
Otake, Yoichi
Koyama, Atsuko
Nishio, Kazuto
Nakagawa, Kazuhiko
author_sort Matsuoka, Hiromichi
collection PubMed
description BACKGROUND: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group. A biomarker for selection of opioids for cancer pain relief would be particularly useful clinically, and therefore we have planned a randomized comparative study of morphine and oxycodone, using the COMT rs4680 SNP as a biomarker. This study is aimed at verifying the assumption that patients in the GG group require an increased morphine dose for pain relief. METHODS: The RELIEF study is a randomized, multi-institutional, open-label trial with a primary endpoint of the proportion of subjects requiring high-dose opioids, as calculated from the dose of a rescue preparation administered on day 0. Secondary endpoints include the Hospital Anxiety and Depression Scale, Short form McGill Pain Questionnaire-2, European Organization for Research and Treatment of Cancer QLQ-C15-PAL, Pain Catastrophizing Scale, and adverse events, Eligibility criteria are patients with advanced carcinoma with non-daily use of opioids in initial screening for registration; and cancer pain targeted for daily opioid treatment, NSAIDs or acetaminophen, NRS ≥3(average over 24 h), opioid-treatment naive within 30 h, no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and written informed consent at the time of second registration. Between November 2014 and June 2017, an estimated 110 patients from two sites in Japan were randomized (1:1) to morphine or oxycodone in GG and non-GG groups. DISCUSSION: A method for selection of appropriate opioids in cancer patients is a high unmet medical need. This study was designed to evaluate the efficacy of different opioids in patients with cancer based on gene polymorphism, as the first potential multi-institutional registration trial to be conducted in cancer patients with pain. TRIAL REGISTRATION: UMIN000015579 Date of registration: 4 November 2014. It is updated once every six months, the latest update is 30 June 2017. Trial status. The enrollment started in November 2014. At the time of manuscript submission (July 2017), Three-quarters of patients have participated. We thus expect to complete the recruitment by March 2018.
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spelling pubmed-56395902017-10-18 Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study) Matsuoka, Hiromichi Tsurutani, Junji Chiba, Yasutaka Fujita, Yoshihiko Terashima, Masato Yoshida, Takeshi Sakai, Kiyohiro Otake, Yoichi Koyama, Atsuko Nishio, Kazuto Nakagawa, Kazuhiko BMC Cancer Study Protocol BACKGROUND: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group. A biomarker for selection of opioids for cancer pain relief would be particularly useful clinically, and therefore we have planned a randomized comparative study of morphine and oxycodone, using the COMT rs4680 SNP as a biomarker. This study is aimed at verifying the assumption that patients in the GG group require an increased morphine dose for pain relief. METHODS: The RELIEF study is a randomized, multi-institutional, open-label trial with a primary endpoint of the proportion of subjects requiring high-dose opioids, as calculated from the dose of a rescue preparation administered on day 0. Secondary endpoints include the Hospital Anxiety and Depression Scale, Short form McGill Pain Questionnaire-2, European Organization for Research and Treatment of Cancer QLQ-C15-PAL, Pain Catastrophizing Scale, and adverse events, Eligibility criteria are patients with advanced carcinoma with non-daily use of opioids in initial screening for registration; and cancer pain targeted for daily opioid treatment, NSAIDs or acetaminophen, NRS ≥3(average over 24 h), opioid-treatment naive within 30 h, no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and written informed consent at the time of second registration. Between November 2014 and June 2017, an estimated 110 patients from two sites in Japan were randomized (1:1) to morphine or oxycodone in GG and non-GG groups. DISCUSSION: A method for selection of appropriate opioids in cancer patients is a high unmet medical need. This study was designed to evaluate the efficacy of different opioids in patients with cancer based on gene polymorphism, as the first potential multi-institutional registration trial to be conducted in cancer patients with pain. TRIAL REGISTRATION: UMIN000015579 Date of registration: 4 November 2014. It is updated once every six months, the latest update is 30 June 2017. Trial status. The enrollment started in November 2014. At the time of manuscript submission (July 2017), Three-quarters of patients have participated. We thus expect to complete the recruitment by March 2018. BioMed Central 2017-10-06 /pmc/articles/PMC5639590/ /pubmed/28985716 http://dx.doi.org/10.1186/s12885-017-3664-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Matsuoka, Hiromichi
Tsurutani, Junji
Chiba, Yasutaka
Fujita, Yoshihiko
Terashima, Masato
Yoshida, Takeshi
Sakai, Kiyohiro
Otake, Yoichi
Koyama, Atsuko
Nishio, Kazuto
Nakagawa, Kazuhiko
Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)
title Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)
title_full Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)
title_fullStr Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)
title_full_unstemmed Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)
title_short Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)
title_sort selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (relief study)
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639590/
https://www.ncbi.nlm.nih.gov/pubmed/28985716
http://dx.doi.org/10.1186/s12885-017-3664-z
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