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Cancer-related breathlessness: opioids other than morphine – comprehensive literature review
  1. Tatsuma Sakaguchi1,2
  1. 1Department of Palliative Care, Kitano Hospital, Osaka, Japan
  2. 2Palliative Care Centre, Aichi Medical University, Nagakute, Japan
  1. Correspondence to Dr Tatsuma Sakaguchi, Palliative Care Centre, Aichi Medical University, Nagakute, 480-1195, Japan; sakaguchi.tatsuma{at}


Introduction Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine.

Methods The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded.

Results A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs.

Conclusion As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.

  • Dyspnoea
  • Cancer

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  • Contributors TS contributed to the conception, acquisition and analysis of data, drafting, and final approval of the manuscript.

  • Funding This research was supported by a grant from the Osaka Cancer Society in 2021.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.