Journal Article

Morphine Versus Oxycodone for Cancer Pain Using a Catechol-O-methyltransferase Genotype Biomarker: A Multicenter, Randomized, Open-Label, Phase III Clinical Trial (RELIEF Study)

Chiba, Yasutaka, Sakamoto, Ryo, Sakai, Kiyohiro, Ohtake, Yoichi, Haratani, Koji, Nakagawa, Kazuhiko, Tsurutani, Junji, Makimura, Chihiro, Nishio, Kazuto, Matsuoka, Hiromichi, Fujita, Yoshihiko, Takeda, Masayuki, Okuno, Tatsuya, Yoshida, Takeshi, Koyama, Atsuko, Hayashi, Hidetoshi, Nakura, Miki, Takegawa, Naoki, Tanaka, Kaoru

2023

Overview

Abstract Background 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. Methods A randomized, multicenter, open-label trial was conducted at a Japanese hospital’s 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 ≥ 33% from baseline and up to ≤ 3 on a numerical rating scale). The primary endpoint was the proportion of subjects requiring high-dose opioids on day 0 with the GG genotype. Results 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 = .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 = 0.098). Conclusion Using the COMT rs4680 genotype alone is not recommended for selecting between morphine and oxycodone for pain relief. This report evaluates the potential for the COMT rs4680 genotype to serve as a biomarker for opioid choice.

• Publisher: Oxford University Press
• Subject: Analgesics, Opioid - adverse effects / Analgesics, Opioid - therapeutic use / Biological markers / Biomarkers / Cancer / Cancer pain / Cancer Pain - drug therapy / Cancer Pain - genetics / Care and treatment / Catechin / Catechol O-Methyltransferase - genetics / Catechol O-Methyltransferase - therapeutic use / Central nervous system depressants / Clinical Trial Results / Clinical trials / Comparative analysis / Dosage and administration / Drug therapy / Drugs / Evidence-based medicine / Genes / Genotype / Genotype & phenotype / Humans / Identification and classification / Medical research / Medicine, Experimental / Morphine / Morphine - therapeutic use / Narcotics / Neoplasms - complications / Neoplasms - drug therapy / Neoplasms - genetics / Oxycodone / Oxycodone - adverse effects / Oxycodone - therapeutic use / Pain / Pain - etiology / Pain - genetics / Palliative care / Palliative treatment / Product development / Transferases