Extended‐release opioids in the management of cancer pain: A systematic review of efficacy and safety

Abstract

Despite the increased availability of strong analgesics and evidence-based recommendations for pain management, under-treatment of cancerrelated pain is still common. Extended-release (ER) opioids, in contrast to immediate-release opioids, provide prolonged analgesia. In this review, we aimed to compare the efficacy and safety of ER opioid analgesics in managing moderate-to-severe pain in patients with cancer. We identified randomized controlled trials (RCTs) and controlled observational studies that compared ER opioids in cancer pain by searching several databases, including MEDLINE, EMBASE and the Cochrane Library. Two independent reviewers screened and evaluated retrieved records to select relevant studies. We dually assessed the risk of bias for included studies and evaluated the overall strength of evidence for six critical outcomes using Grading of Recommendations Assessment, Development and Evaluation level of evidence. A total of three double-blind RCTs (comparative efficacy and adverse events), two non-blinded RCTs and four observational studies (comparative adverse events) were included in this review. All randomized trials and one observational study were of high risk of bias, and three observational studies of unclear risk of bias. The level of evidence for the selected efficacy and safety outcomes was low and very low. We synthesized the findings qualitatively because of the paucity of relevant studies as well as variable study design and quality. This systematic review indicates no substantial differences in efficacy and frequent adverse events among ER opioids for cancer pain. The body of evidence, however, is limited to few comparisons and fraught with methodological shortcomings.

Strong opioids for noncancer pain due to musculoskeletal diseases: Not more effective than acetaminophen or NSAIDs

“…Furthermore, recent opioids such as oxycodone (Oxycontin ® , Oxynorm ® ) or hydromorphone (Sophidone ® ) were not more effective than morphine [32]. Similarly, although several recommendations indicate that preference should be given to sustained-release forms, the six randomized trials that compared sustained-release to immediate-release opioids found no difference [33] in efficacy or adverse events, particularly addiction, both in noncancer pain and in cancer pain [34].…”

A third of systematic reviews changed or did not specify the primary outcome: a PROSPERO register study

“…Limited resources meant that we were unable to contact authors of the discrepant systematic reviews to determine the reason for these inconsistencies. Only one review reported a rationale for changing the outcome, which makes it difficult to provide definitive conclusions as to why these changes may occur [15]. The reason that was reported by the authors was that the clinical experts on their team selected the most clinically important outcomes, which did not align with what was reported in their PROSPERO record.…”

PCL microsphere/PEG‐based composite hydrogels for sustained release of methadone hydrochloride

“…Potential solutions to this problem are extended‐release formulations, localized and topical delivery of opioids directly to the wound site via wound dressing. Extended‐release formulations were fabricated in order to keep plasma drug concentration within the therapeutic window for a long time while reducing the risk of side effects and toxicity . Thus, the development of controlled drug‐delivery systems is necessary to achieve sustained pain relief .…”