Opioids for cancer pain ‐ an overview of Cochrane reviews

Background Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine‐like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly‐used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol. Objectives To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use. Methods We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events. Main results We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes. Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both. Reviews o