Opioids for cancer-related pain in children and adolescents

Bottom line

There is no evidence from randomised controlled trials to support or contradict the suggestion that opioids in any dose will reduce cancer-related pain in children or adolescents.

Background

Childhood cancer is one of the leading causes of disease and death for children and adolescents in the world today. Its associated pain is a major health concern and specific data for children are not currently well known. Cancer-related pain is generally caused directly by a tumour compressing on nerves or by organ inflammation, and can very distressing.

Opioids are used worldwide for the treatment of pain. Opioids are generally available in healthcare settings across most developed countries but access may be restricted in developing countries. For example, currently available opioids include: buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol. Opioids are used in varying doses and commonly administered via injection or oral tablets.

Key results

In February 2017 we searched for clinical trials where any opioids were used to treat cancer-related pain in people aged from birth to 17 years. We found no studies that met the requirements for this review. Several studies tested opioids on adults with cancer-related pain, but none in participants aged from birth to 17 years.

Quality of the evidence

We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low quality evidence means that we are very uncertain about the results. High quality evidence means that we are very confident in the results.

We rate the quality of evidence as very low. Due to a lack of data, there is no evidence from randomised controlled trials to support or contradict the suggestion that opioids in any dose will reduce cancer-related pain in children or adolescents.

Authors' conclusions: 

No conclusions can be drawn about efficacy or harm in the use of opioids to treat cancer-related pain in children and adolescents. As a result, there is no RCT evidence to support or refute the use of opioids to treat cancer-related pain in children and adolescents.

Read the full abstract...
Background: 

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences.

We designed a suite of seven reviews in chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) to review the evidence for children's pain using pharmacological interventions.

As one of the leading causes of mortality and morbidity for children and adolescents in the world today, childhood cancer (and its associated pain) is a major health concern. Cancer pain in infants, children, and adolescents is primarily nociceptive pain with negative long term effects. Cancer-related pain is generally caused directly by the tumour itself such as compressing on the nerve or inflammation of the organs. Cancer-related pain generally occurs as a result of perioperative procedures, nerve damage caused by radiation or chemotherapy treatments, or mucositis. However, this review focused on pain caused directly by the tumour itself such as nerve infiltration, external nerve compression, and other inflammatory events.

Opioids are used worldwide for the treatment of pain. Currently available opioids include: buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol. Opioids are generally available in healthcare settings across most developed countries but access may be restricted in developing countries. To achieve adequate pain relief in children using opioids, with an acceptable grade of adverse effects, the recommended method is to start with a low dose gradually titrated to effect or unacceptable adverse effect in the child.

Objectives: 

To assess the analgesic efficacy, and adverse events, of opioids used to treat cancer-related pain in children and adolescents aged between birth and 17 years, in any setting.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid and Embase via Ovid from inception to 22 February 2017. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.

Selection criteria: 

Randomised controlled trials (RCTs), with or without blinding, of any dose, and any route, treating cancer-related pain in children and adolescents, comparing opioids with placebo or an active comparator.

Data collection and analysis: 

Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table.

Main results: 

No studies were identified that were eligible for inclusion in this review (very low quality evidence). Several studies tested opioids on adults with cancer-related pain, but none in participants aged from birth to 17 years.

We rated the quality of evidence as very low, downgraded due to a lack of available data; no analyses could be undertaken.

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