Aims: To evaluate the evidence on the benefits and harms of opioid medicines compared to placebo, other analgesics or non-pharmacological interventions for people with background and breakthrough cancer-related pain.
Methods: Electronic databases including the Cochrane Library, Medline EMBASE and PsycINFO were searched for systematic reviews, clinical trials, cohort studies or clinical guidelines up to February 2023 evaluating the benefits and/or harms of opioids for background or breakthrough cancer pain.
Results: There are few placebo-controlled trials evaluating opioids for cancer pain in adults. Currently, there is moderate-to-low certainty evidence that tapentadol or codeine may provide better pain relief than placebo for background cancer pain. Selected non-steroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac or ketorolac, and the antidepressant medicine imipramine are at least as efficacious as opioids for background cancer pain. Oral transmucosal, buccal, sublingual or intranasal fentanyl were all found to be more efficacious than placebo for breakthrough cancer pain, but were associated with more adverse effects including nausea and constipation. Although it is widely recommended as first line treatment in international guidelines, based on the current evidence morphine was generally not found to be superior to other opioids, nor was it considered to be safer. There was large heterogeneity in the studies, which makes interpretation and translation of study findings challenging. There is emerging in-vitro and preclinical evidence to suggest that certain opioids, including morphine, may affect the body’s ability to fight cancer. However the clinical implications needs to be explored rigorously in future studies.
Conclusion: There is limited evidence evaluating the efficacy of opioids compared with placebo for cancer pain in adults. This likely reflects the ethical and logistical challenges associated with carrying out these trials. Given the limited quantity and quality of data available, there is a need to reappraise the clinical utility of opioids for cancer pain.