Elsevier

The Lancet Oncology

Volume 13, Issue 2, February 2012, Pages e58-e68
The Lancet Oncology

Review
Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC

https://doi.org/10.1016/S1470-2045(12)70040-2Get rights and content

Summary

Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system.

Introduction

Moderate to severe pain in cancer is common and affects 70–80% of patients with advanced disease. We have the means and the knowledge to relieve most pain in cancer for most patients,1 but evidence from surveys and observational studies shows that many patients have troublesome or severe pain and do not get adequate relief.2

The skilled use of opioid analgesics is crucial to the relief of cancer pain, but there is a shocking lack of evidence to support clinical practice. The so-called analgesic ladder is the central idea of the WHO 1996 guidelines on cancer pain relief,3 in which the choice of analgesic is determined by the severity of the pain. The WHO method has been adopted worldwide but the lack of up-to-date evidence, knowledge, and opioid availability have obstructed the path to effective relief of cancer pain.2, 4

Randomised controlled trials (RCTs) in patients with cancer pain are beset by difficulties.5 In the absence of hard evidence from RCTs, expert consensus and clinical guidelines might be helpful, because cancer pain relief is a specialist area but most care is delivered by non-specialist practitioners. The European Association for Palliative Care (EAPC) research network published its first guidelines on the use of morphine and alternative opioids in cancer pain in 1996,6 and published an update in 2001.7 In this Review we present further work done to strengthen the scope of the EAPC recommendations by the application of rigorous, evidence-based methodology.

Section snippets

Development of recommendations

A comprehensive list of relevant topics on opioid use for cancer pain was derived from a comparison of the previous EAPC recommendations with other available guidelines on cancer pain relief. This list was submitted to a formalised expert consensus process that led to 30 practical clinical questions being summarised in 22 topics.8, 9 The subsequent guidelines development process followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.10, 11, 12, 13

Each of

Findings

Step II opioids (table 1) have been traditionally used for moderate cancer pain. The systematic review showed that codeine and tramadol are effective compared with placebo.15 The analgesic effect of paracetamol in conjunction with codeine was shown in an RCT34 that compared 150 mg codeine alone with 60 mg codeine plus 600 mg paracetamol, and showed that the combination four times per day was as effective and safe as codeine alone twice daily.

Only one RCT provided direct comparative data for the

Discussion

The guidelines we present are the product of an international European Palliative Care Research Collaborative project aimed at revising previous EAPC recommendations for use of opioids to treat cancer pain.7 We used a stepwise process8, 9 combined with a systematic literature review strategy. In view of the long-standing experience with opioid analgesics, the overall poverty of the evidence underlying many features of their use is surprising.

The quality and the content of the most recent

Search strategy and selection criteria

We did a systematic search for English-language randomised and non-randomised trials and meta-analyses that involved human adults with chronic cancer pain and contained data on efficacy, side-effects, or both, of the treatment considered and described relevant outcomes associated with each topic. We electronically searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from the inception of each database to July 31, 2009. The search terms were text words and MeSH/EMTREE

References (94)

  • GK Gourlay

    Treatment of cancer pain with transdermal fentanyl

    Lancet Oncol

    (2001)
  • S Mercadante et al.

    Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management

    Eur J Pain

    (2008)
  • P Poulain et al.

    Efficacy and safety of transdermal buprenorphine: a randomized, placebo-controlled trial in 289 patients with severe cancer pain

    J Pain Symptom Manage

    (2008)
  • V Ventafridda et al.

    A randomized study on oral administration of morphine and methadone in the treatment of cancer pain

    J Pain Symptom Manage

    (1986)
  • RG Twycross

    Choice of strong analgesic in terminal cancer: diamorphine or morphine?

    Pain

    (1977)
  • H Knotkova et al.

    Opioid rotation: the science and the limitations of the equianalgesic dose table

    J Pain Symptom Manage

    (2009)
  • S Grond et al.

    Transdermal fentanyl in the long-term treatment of cancer pain: a prospective study of 50 patients with advanced cancer of the gastrointestinal tract or the head and neck region

    Pain

    (1997)
  • DF Zech et al.

    Transdermal fentanyl and initial dose-finding with patient-controlled analgesia in cancer pain. A pilot study with 20 terminally ill cancer patients

    Pain

    (1992)
  • BR Ferrell et al.

    The role of patient-controlled analgesia in the management of cancer pain

    J Pain Symptom Manage

    (1992)
  • MC Vanier et al.

    Comparison of hydromorphone continuous subcutaneous infusion and basal rate subcutaneous infusion plus PCA in cancer pain: a pilot study

    Pain

    (1993)
  • G Meuret et al.

    Patient-controlled analgesia (PCA) in the domiciliary care of tumour patients

    Cancer Treat Rev

    (1996)
  • AN Davies et al.

    The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland

    Eur J Pain

    (2009)
  • DF Haugen et al.

    Assessment and classification of cancer breakthrough pain: a systematic literature review

    Pain

    (2010)
  • HG Kress et al.

    Efficacy and tolerability of intranasal fentanyl spray 50 to 200 μg for breakthrough pain in patients with cancer: a phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10-month, open-label extension treatment period

    Clin Ther

    (2009)
  • S Mercadante et al.

    Intravenous morphine for breakthrough (episodic-) pain in an acute palliative care unit: a confirmatory study

    J Pain Symptom Manage

    (2008)
  • RK Portenoy et al.

    Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study

    J Pain Symptom Manage

    (2008)
  • V Ventafridda et al.

    A validation study of the WHO method for cancer pain relief

    Cancer

    (1987)
  • Cancer pain relief

    (1996)
  • Morphine in cancer pain: modes of administration

    BMJ

    (1996)
  • GW Hanks et al.

    Morphine and alternative opioids in cancer pain: the EAPC recommendations

    Br J Cancer

    (2001)
  • A Pigni et al.

    Content development for EUROPEAN GUIDELINES on the use of opioids for cancer pain: a systematic review and Expert Consensus Study

    Minerva Anestesiol

    (2010)
  • GH Guyatt et al.

    GRADE: an emerging consensus on rating quality of evidence and strength of recommendations

    BMJ

    (2008)
  • GH Guyatt et al.

    What is “quality of evidence” and why is it important to clinicians?

    BMJ

    (2008)
  • GH Guyatt et al.

    Going from evidence to recommendations

    BMJ

    (2008)
  • GH Guyatt et al.

    Incorporating considerations of resources use into grading recommendations

    BMJ

    (2008)
  • A Caraceni et al.

    Is oral morphine still the first choice opioid for moderate to severe cancer pain? A systematic review within the European Palliative Care Research Collaborative guidelines project

    Palliat Med

    (2011)
  • D Tassinari et al.

    The second step of the analgesic ladder and oral tramadol in the treatment of mild to moderate cancer pain: a systematic review

    Palliat Med

    (2011)
  • P Klepstad et al.

    Starting step III opioids for moderate to severe pain in cancer patients: dose titration: a systematic review

    Palliat Med

    (2011)
  • P Stone et al.

    European Palliative Care Research collaborative pain guidelines. Central side-effects management: what is the evidence to support best practice in the management of sedation, cognitive impairment and myoclonus?

    Palliat Med

    (2011)
  • EA Laugsand et al.

    Management of opioid-induced nausea and vomiting in cancer patients: systematic review and evidence-based recommendations

    Palliat Med

    (2011)
  • SJ King et al.

    A systematic review of oxycodone in the management of cancer pain

    Palliat Med

    (2011)
  • A Pigni et al.

    The role of hydromorphone in cancer pain treatment: a systematic review

    Palliat Med

    (2011)
  • D Tassinari et al.

    Transdermal opioids as front line treatment of moderate to severe cancer pain: a systemic review

    Palliat Med

    (2011)
  • N Cherny

    Is oral methadone better than placebo or other oral/transdermal opioids in the management of pain?

    Palliat Med

    (2011)
  • O Dale et al.

    European Palliative Care Research Collaborative pain guidelines: opioid switching to improve analgesia or reduce side effects. A systematic review

    Palliat Med

    (2011)
  • S Mercadante et al.

    Conversion ratios for opioid switching in the treatment of cancer pain: a systematic review

    Palliat Med

    (2011)
  • G Zeppetella

    Opioids for the management of breakthrough cancer pain in adults: a systematic review undertaken as part of an EPCRC opioid guidelines project

    Palliat Med

    (2011)
  • Cited by (0)

    These authors contributed equally

    View full text