Buprenorphine for treating people with cancer pain

Buprenorphine produced good pain relief for most people with moderate or severe cancer pain, but its role in the treatment of cancer pain is still unclear.

Many patients with cancer experience moderate-to-severe pain that requires treatment with strong pain relief medicines. Buprenorphine and morphine are examples of strong pain relief medicines that are used for the relief of cancer pain. However, strong pain relief medicines are not effective for pain in all patients nor are they well-tolerated by all patients. The aim of this Cochrane review is to assess whether buprenorphine is associated with better, worse or equal pain relief and tolerability compared to other pain relief medicines for patients with cancer pain.

We searched the literature on 20 Janurary 2015 and found 19 relevant studies with a total of 1421 patients that compared different types of buprenorphine to each other or to other strong pain relief medicines or to placebo. The reported average ages of the patients ranged from 49.1 years to 67.16 years, and the duration of the studies ranged from single dose treatment to six months.

Generally, the studies showed that buprenorphine is an effective strong pain relief medicine that in some cases may be slightly better than other strong pain relief medicines. However, the evidence provided by these studies were of very low quality and on the basis of the available evidence, it is still hard to say where buprenorphine fits in in the treatment of cancer pain with strong opioids. All the strong pain relief medicines examined in the studies are also associated with a number of unwanted effects, such as vomiting, constipation and drowsiness.

Authors' conclusions: 

Based on the available evidence, it is difficult to say where buprenorphine fits in the treatment of cancer pain with strong opioids. However, it might be considered to rank as a fourth-line option compared to the more standard therapies of morphine, oxycodone and fentanyl, and even there it would only be suitable for some patients. However, palliative care patients are often heterogeneous and complex, so having a number of analgesics available that can be given differently increases patient and prescriber choice. In particular, the sublingual and injectable routes seemed to have a more definable analgesic effect, whereas the transdermal route studies left more questions.

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Background: 

Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong opioids used for the relief of cancer pain. Strong opioids are, however, not effective for pain in all patients nor are they well-tolerated by all patients. The aim of this Cochrane review is to assess whether buprenorphine is associated with superior, inferior or equal pain relief and tolerability compared to other analgesic options for patients with cancer pain.

Objectives: 

To assess the effectiveness and tolerability of buprenorphine for pain in adults and children with cancer.

Search strategy: 

We searched CENTRAL (the Cochrane Library) issue 12 or 12 2014, MEDLINE (via OVID) 1948 to 20 January 2015, EMBASE (via OVID) 1980 to 20 January 2015, ISI Web of Science (SCI-EXPANDED & CPCI-S) to 20 January 2015, ISI BIOSIS 1969 to 20 January 2015. We also searched ClinicalTrials.gov (http://clinicaltrials.gov/; metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/) and the Proceedings of the Congress of the European Federation of International Association for the Study of Pain (IASP; via European Journal of Pain Supplements) on 16 February 2015. We checked the bibliographic references of identified studies as well as relevant studies and systematic reviews to find additional trials not identified by the electronic searches. We contacted authors of included studies for other relevant studies.

Selection criteria: 

We included randomised controlled trials, with parallel-group or crossover design, comparing buprenorphine (any formulation and any route of administration) with placebo or an active drug (including buprenorphine) for cancer background pain in adults and children.

Data collection and analysis: 

Two review authors independently extracted data pertaining to study design, participant details (including age, cancer characteristics, previous analgesic medication and setting), interventions (including details about titration) and outcomes, and independently assessed the quality of the included studies according to standard Cochrane methodology. As it was not feasible to meta-analyse the data, we summarised the results narratively. We assessed the overall quality of the evidence for each outcome using the GRADE approach.

Main results: 

In this Cochrane review we identified 19 relevant studies including a total of 1421 patients that examined 16 different intervention comparisons.

Of the studies that compared buprenorphine to another drug, 11 studies performed comparative analyses between the randomised groups, and five studies found that buprenorphine was superior to the comparison treatment. Three studies found no differences between buprenorphine and the comparison drug, while another three studies found treatment with buprenorphine to be inferior to the alternative treatment in terms of the side effects profile or patients preference/acceptability.

Of the studies that compared different doses or formulations/routes of administration of buprenorphine, pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository. However, the average severity of dizziness, nausea, vomiting and adverse events as a total were all significantly higher in the intramuscular group relatively to the suppository group (one study).

Sublingual buprenorphine was associated with faster onset of pain relief compared to subdermal buprenorphine, with similar duration analgesia and no significant differences in adverse event rates reported between the treatments (one study).

In terms of transdermal buprenorphine, two studies found it superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine.

The studies that examined different doses of transdermal buprenorphine did not report a clear dose-response relationship.

The quality of this evidence base was limited by under-reporting of most bias assessment items (e.g., the patient selection items), by small sample sizes in several included studies, by attrition (with data missing from 8.2% of the enrolled/randomised patients for efficacy and from 14.6% for safety) and by limited or no reporting of the expected outcomes in a number of cases. The evidence for all the outcomes was very low quality.

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