Caraceni, A., Hanks, G., Kaasa, S., Bennett, M.I., Brunelli, C., Cherny, N., . . . European Association for Palliative Care (EAPC). (2012). Use of opioid analgesics in the treatment of cancer pain: Evidence-based recommendations from the EAPC. Lancet Oncology, 13, e58–e68.

The guidelines, which relate to the use of opioids to treat cancer pain, are the result of revision of previous European Palliative Care Research Collaborative guidelines.

• In the development of the revised guidelines, collaborators assigned 22 topics to groups of reviewers, who completed the systematic review using a standardized method. The evidence profile of each relevant outcome was reviewed and became the basis of the final recommendations. The Scientific Advisory Board of the European Palliative Care Research Collaborative and the Board of Directors of the European Association for Palliative Care reviewed the recommendations. Upon revision, the recommendations were again distributed to the groups for comment and/or approval.
• The data search completed in connection with the project was a systematic retrieval of randomized and nonrandomized trials and meta-analyses that
  • Involved adults with chronic cancer pain
  • Contained data on efficacy, side effects, and the treatments considered
  • Described outcomes.
• Databases searched were MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL).
• Search keywords were terms relevant to each outcome. Outcomes related to the following: World Health Organization (WHO) step II opioids, WHO step III opioid of first choice, opioid titration, role of transdermal opioids, role of methadone, opioid switching, relative opioid analgesic potencies, alternative systemic routes of opioid administration, opioids for breakthrough pain, treatment of opioid-related emesis, treatment of opioid-related constipation, treatment of opioid-related central nervous system symptoms, use of opioids in patients with renal failure, role of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to step III opioids, role of adjuvant drugs for neuropathic pain (antidepressants and anticonvulsants), and spinal route of opioid administration.
• Studies were excluded if they dealt with the role of opioids in liver failure and the use of opioid combinations. (Data were of insufficient quality to support a recommendation regarding these topics.) Reviewers excluded a literature review regarding the treatment of opioid-related constipation; its content completely overlapped that of a Cochrane review. The role of ketamine was not included because resources to complete the work were unavailable.
• Authors made 16 recommendations based on evidence profiles.

• Patients were undergoing multiple phases of care.
• The study has clinical applicability for palliative care, late effects and survivorship, and elder care.

Findings are submitted as a general framework to help clinicians make informed decisions regarding cancer pain management.

• Data reveal no differences regarding the use of morphine, oxycodone, and hydromorphone; any can be used as step III treatment.
• Guidelines include a weak recommendation regarding oral opioids:
  • Immediate- and slow-release oral opioids can be used for dose titration.
  • Transdermal fentanyl and buprenorphine are step III alternatives, and some patients may prefer them.
  • Methadone can be used as a step III opioid but only by experienced providers, given its complex pharmacokinetic profile.
• Guidelines include a weak recommendation regarding patients who are not getting adequate analgesia: These patients may benefit from opioid switching.
• Guidelines include strong recommendations regarding route of administration:
  • The subcutaneous route should be the first choice when alternate routes of administration are needed.
  •  Breakthrough pain can be managed with oral, immediate-release opioids or buccal or intranasal fentanyl.
• Guidelines include a weak recommendation about additions to step III opioids: Add NSAIDs or paracetamol to step III opioids. However, guidelines note that efficacy is not well documented.
• Guidelines include a strong recommendation regarding neuropathic pain: Consider using amitriptyline or gabapentin for patients with neuropathic pain that is only partially responsive to opioids. 
• Guidelines include a weak recommendation regarding epidural and intrathecal opioids: Consider using an epidural or intrathecal opioid with a local anesthetic in cases of intractable pain or intolerable adverse effects.

• Pharmaceutical industry sponsorships were noted.
• The guidelines do not evaluate treatment costs.
• The process evidenced lack of consensus regarding methods of pain assessment.