NSAIDs for cancer-related pain in children and adolescents

Bottom line

We are uncertain whether NSAIDs will provide pain relief for 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 pain in infants, children, and adolescents is primarily nerve pain with negative long term effects. Cancer-related pain is generally caused directly by the tumour itself such as nerve infiltration, external nerve compression, and other inflammatory events.

NSAIDs are used to treat pain or reduce fever, and are commonly used in children. NSAIDs are currently licensed for use in western countries, but they are not approved for infants aged under three months. The key side effects of NSAIDs are stomach problems and possible damage to kidneys following long term use. Other side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, flatulence, stomach pain, and indigestion.

Key results

In February 2017 we searched for randomised controlled clinical trials where any NSAIDs were used to treat any 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 NSAIDs on adults in chronic 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 overall quality of evidence to be very low quality evidence due to a lack of information, meaning there is no evidence to support or refute the use of NSAIDs.

Authors' conclusions: 

There is no evidence from randomised controlled trials that non-steroidal anti-inflammatory drugs (NSAIDs) reduce cancer-related pain in children and adolescents. This means that no reliance or conclusions can be made about efficacy or harm in the use of NSAIDs to treat chronic 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 persisting pain in children 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 as priority areas) 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. Specific mortality and morbidity data relating to children are not currently identified. All childhood cancer rates are on the rise; for example, in the USA approximately 10,380 children aged under 15 years were expected to be diagnosed with cancer by the end of 2016. However, with survival rates also increasing, over 80% of paediatric cancer patients are expected to survive for five years or more, thus identifying the need to address pain management in this population.

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.

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammatory properties. They are commonly used within paediatric pain management. NSAIDs are currently licensed for use in western countries, however not approved for infants aged under three months. Primary adverse effects include gastrointestinal issues and possible renal impairment with long term use. Other adverse effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain.

Objectives: 

To assess the analgesic efficacy, and adverse events, of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat cancer-related pain in children and adolescents aged from 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 21 February 2017. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.

Selection criteria: 

Randomised, double-blind trials of any dose, and any route, treating cancer-related pain in children and adolescents, comparing NSAIDs 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 eligible for inclusion in this review (very low quality evidence). We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome.

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