The role of transdermal buprenorphine in the treatment of cancer pain: an expert panel consensus

ABSTRACT

Background: The semi-synthetic opioid, buprenorphine, has the general structure of morphine but differs from it in significant ways, both pharmacologically and clinically. A number of long-term studies have shown effective, long-lasting analgesia in moderate to severe cancer and non-cancer pain, including neuropathic pain, with a low incidence of constipation, nausea, dizziness and tiredness. The treatment of moderate to severe chronic pain has improved as a result of the development of new methods of administration of this substance, particularly the introduction of the transdermal drug delivery system, which offers a number of advantages over the usual oral and parenteral routes.

Scope: A panel of experts specialising in palliative care and pain treatment was convened in November 2007 to discuss their clinical experiences with transdermal buprenorphine and other analgesics. The aim was to provide practical guidance on the treatment of cancer pain with transdermal buprenorphine, particularly when there is a need for increasing pain relief leading to high and increasing doses. A literature search on the use of transdermal buprenorphine was carried out for the panel meeting (based on a search of PubMed to November 2007 – since updated by an additional search for the period to February 2009) and a number of case histories were presented and discussed. This commentary article presents this evidence and the consensus findings of the expert panel.

Findings: The Panel reached consensus that transdermal buprenorphine was a valuable treatment for chronic cancer pain, including its neuropathic components. A number of general recommendations were made. Large-scale, randomised clinical studies are needed to provide product comparisons on the use of analgesics in the treatment of neuropathic pain although it was recognised that such studies may not be practicable. Data on the treatment of acute and chronic pain should be kept separate in general. Physicians should be made more aware of the problem of hyperalgesic effects of some opioids in long term use. Buprenorphine in contrast has been described to exert an antihyperalgesic effect. The development of analgesic tolerance with some opioids in long term use and the lack of it with buprenorphine requires further studies. The registered dose range of 35–140 µg/h was considered adequate to achieve sufficient pain relief in most patients although some members of the panel presented data showing that increases beyond this dose range provided improved pain relief if slow titration is used. However, it was generally felt that more evidence was needed before this could become generally acceptable.

Conclusion: The consensus was that transdermal buprenorphine has a valuable role to play in the treatment of chronic cancer pain because of its efficacy and good safety and tolerability profile, including a low risk of respiratory depression, a lack of immunosuppression and a lack of accumulation in patients with impaired renal function.

Key words: :

• Cancer pain
• Neuropathic pain
• Opioid
• Palliative care
• Transdermal buprenorphine analgesic

Transparency

Declaration of funding

The material in this article was previously presented at an expert panel meeting held in Marseille, France on 30 November 2007. The authors' attendance at the meeting and the medical writing support provided by Euromed Communications were funded by Grünenthal GmbH (the licence holder of the branded transdermal buprenorphine, Transtec). The views expressed in this consensus statement are those of the expert panel and not necessarily those of the meeting sponsor.

Declaration of financial/other relationships

J.V.P., the meeting chair and corresponding author of the article, has disclosed that he has received an honorarium for serving on the advisory board of Grünenthal. None of the other authors have disclosed a financial relationship with Grünenthal in addition to that above but have disclosed that they have given talks, attended conferences and participated in trials and advisory boards sponsored by various other pharmaceutical companies.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed he/she is a former employee and stockholder of AstraZeneca Pharmaceuticals Ltd and a consultant/advisor to a medical communications company on regulatory issues. Peer Reviewer 2 has disclosed he/she has no relevant financial relationships.

Acknowledgments

The authors acknowledge the medical writing support and editorial assistance of Joe Ridge of Euromed Communications, which was financially supported by Grünenthal.