Poster Presentation 2025 Joint Meeting of the COSA ASM and IPOS Congress

A feasibility randomised controlled trial comparing opioid dose escalation vs methadone addition for refractory cancer pain (126141)

Takako Ikegami 1 2 , Hiromichi Matsuoka 3 4 , Kosuke Terada 5 , Shunsuke Oyamada 6 , Keisuke Ariyoshi 7 , Naho Matsubara 2 , Rumi Nishimura 4 , Akiko Abe 4 , Sayaka Arakawa 4 , Hiroto Ishiki 4 , Makoto Maeda 5 , Hironobu Hashimoto 5 , Tomofumi Miura 8 , Hiroshi Ishiguro 9 , Yoshihisa Matsumoto 10 , Eriko Satomi 2 4
  1. Osaka Medical and Pharmaceutical University, Takatsuki City, OSAKA, Japan
  2. Department of Palliative Medicine, National Cancer Center Hospital, Tokyo, Japan
  3. Department of Psycho-oncology,, National Cancer Center Hospital, Tokyo, Japan
  4. Department of Palliative and Supportive Care Development, National Cancer Center Hospital, Tokyo, Japan
  5. Department of Pharmacy,, National Cancer Center Hospital, Tokyo, Japan
  6. Department of Biostatistics, JORTC Data Center, Tokyo, Japan
  7. Department of Data Management, JORTC Data Center, Tokyo, Japan
  8. Department of Palliative Medicine, National Cancer Center East Hospital, Kashiwa city, Chiba, Jaban
  9. Breast Oncology Service, Saitama Medical University International Medical Center, Hidaka city, Saitama, Japan
  10. Department of Palliative Medicine,, Cancer Institute Hospital of JFCR , Tokyo, Japan

Background:

Cancer pain, especially in advanced stages, often includes opioid-refractory and neuropathic components. Although methadone has shown superior efficacy compared to conventional opioids, especially for neuropathic pain, the methadone add-on (AO) method has not yet been evaluated in randomised controlled trials (RCTs).

 

Objective:

To evaluate the feasibility of a double-blind RCT assessing the efficacy and safety of methadone AO in patients with opioid-refractory cancer pain.

 

Methods:

This is a two-centere, double-blind, parallel-group RCT enrolling 22 adults with advanced, unresectable cancer experiencing refractory pain despite receiving 60–300 mg oral morphine equivalent daily dose. Eligible participants (Karnofsky Performance Status ≧50) will be randomised (1:1) to receive either over-encapsulated methadone (5 mg or 10 mg, twice daily) or over-encapsulated oxycodone (10 mg or 20 mg, twice daily), with placebo used to preserve blinding. Assessments will be conducted at baseline(day0), days 1, 8, and 15. The primary endpoint is the treatment completion rate ≥70%. Secondary endpoints include changes in Brief Pain Inventory (BPI) scores and adverse events.

 

Discussion:

Several considerations influenced the study design. The morphine-to-methadone conversion ratio was set at 6:1 to ensure safety while maintaining efficacy, based on previous studies1) and clinical experience. A 2-week study period was chosen, as earlier research has demonstrated that methadone titration stabilises within this timeframe and pain relief can be observed as early as Day 82). The 70% completion rate was determined from prior cohort data and expert consensus as a feasible benchmark for assessing acceptability. This pilot study will provide critical data on recruitment, tolerability, and preliminary efficacy to inform a future large-scale international collaborative RCT aimed at validating methadone AO as a strategy for managing refractory cancer pain.

  1. 1) Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F. Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? J Clin Oncol. 1998;16(10):3216–21.
  2. 2) Bruera E, Palmer JL, Bosnjak S, et al. Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study. J Clin Oncol. 2004 Jan 1;22(1):185-92.