Transdermal fentanyl for cancer pain

Fentanyl patches placed on the skin produced good pain relief for most people with moderate or severe cancer pain.

One person in two or three who gets cancer will suffer from pain that becomes moderate or severe in intensity. The pain tends to get worse as the cancer progresses. Morphine taken by mouth has been used since the 1950s for controlling cancer pain. Since that time a number of different drugs with morphine-like actions have been produced for treating cancer pain, one of which is fentanyl. Fentanyl is particularly useful because it can be absorbed through the skin from patches. The ability of any drug to achieve consistent drug levels in the blood and the brain could, in theory, lead to better control of cancer pain. It also relieves the need to take medicines several times a day, as patches can often last for several days before changing.

We found nine studies involving 1244 patients. The studies were often small, used different study designs, and compared fentanyl with many different drugs. Most patients had pain that went from moderate or severe before transdermal fentanyl to no worse than mild pain when using transdermal fentanyl. Only 3 in 10 patients were constipated using transdermal fentanyl compared with 5 in 10 using oral morphine. We could not analyse the data in a meaningful way regarding harmful (adverse) events such as nausea, abdominal pain, gastrointestinal bleeding, and confusion. These events may have been attributable to the underlying disease processes.

The effect of the patch can continue after it has been taken off due to medicine that has been taken up by the skin. Used patches need to be disposed of carefully.

We could wish for more consistency in study design, and especially in study reporting, which should include the outcome of pain reduced to tolerable levels – no worse than mild pain – so that patients with cancer are not bothered by pain.

Authors' conclusions: 

The randomised trial literature for effectiveness of transdermal fentanyl is limited, but it is an important medicine. Most studies recruited fewer than 100 participants and did not provide data appropriate for meta-analysis. Only a few reported how many patients had good pain relief but, where data were reported, a majority had no worse than mild pain within a reasonably short time period. The evidence pointed to a useful and significant reduction in complaints about constipation for transdermal fentanyl compared with oral morphine.

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Background: 

Opioid drugs have been used for many years to relieve pain. Transdermal fentanyl offers one option for delivering and maintaining pain relief in patients with moderate or severe cancer pain.

Objectives: 

To determine the analgesic efficacy of transdermal fentanyl for relief of cancer pain, and to assess the adverse events associated with the use of transdermal fentanyl for relief of cancer pain.

Search strategy: 

The following databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4 of 12); MEDLINE (1966 to May 2013); EMBASE (1974 to May 2013; CANCERLIT (PubMED) (November 2012); and ClinicalTrials.gov (May 2013).

Selection criteria: 

Published randomised controlled trials (RCTs) using placebo or active comparators reporting on the analgesic effect of transdermal fentanyl in adults and children with cancer pain. Studies with fewer than 10 participants were excluded.

Data collection and analysis: 

Data were extracted independently by two review authors. We extracted any available data on the number or proportion of patients with ‘no worse than mild pain’ or treatment success (very satisfied, or very good or excellent on patient global impression scales), together with information about adverse events and withdrawals.

Main results: 

We identified nine studies meeting the inclusion criteria, including a Turkish study that is awaiting formal translation. There were 1244 participants randomised in classically designed RCTs, of whom 1197 had evaluable data, and 138 patients enrolled in an enriched enrolment, randomised withdrawal (EERW) trial. Overall, 600 participants were treated with transdermal fentanyl patches, 382 with various formulations of morphine, 36 with methadone, and 221 with paracetamol plus codeine. There were major sources of potential bias, including lack of blinding, small size, high levels of attrition, and inconsistent reporting.

We could not compare data in a meaningful analysis regarding adverse events such as nausea, abdominal pain, gastrointestinal bleeding, and confusion. These events may have been attributable to the underlying disease process.

There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers needed to treat (NNT) for the analgesic effect. In seven studies with 461 participants reporting pain intensity results after about two weeks, the mean or median pain scores were on the borderline of mild and moderate pain. Most participants would have had no worse than mild pain on treatment. Another reported that 77% of participants using transdermal fentanyl had an undefined successful outcome. Fewer participants experienced constipation with transdermal fentanyl (28%) than with oral morphine (46%), giving a risk ratio of 0.61 (95% CI 0.47 to 0.78); the NNT to prevent constipation was 5.5 (95% CI 3.8 to 10).

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