Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults

Bottom line

There is no high-quality evidence to prove that NSAIDs are useful in treating people with cancer pain. Nor is there evidence to disprove that they are useful. Very low-quality evidence shows that some people with moderate or severe cancer pain have pain much reduced within one or two weeks.

Background

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. In 1986, the World Health Organization (WHO) recommended taking morphine-like drugs (opioids) for moderate to severe pain from cancer, and non-opioid drugs like NSAIDs, alone for mild to moderate pain, or alongside opioids in people with moderate to severe pain. There are many different types of NSAIDs. Common NSAIDs are ibuprofen and diclofenac.

Study characteristics

In this review we set out to examine the evidence on how well NSAIDs worked (alone or with morphine-like drugs) in adults with cancer pain. We also wanted to know how many people had side effects, and how severe they were.

In April 2017, we found 11 studies with 949 participants. They compared NSAID with NSAID, or NSAID with opioid drug (morphine or codeine). No studies looked at using NSAID together with an opioid-like morphine, which is how they are often used. The studies were small and of poor quality. They used different designs and different ways of showing their pain results. Outcomes important to people with cancer pain were often not reported. Many different NSAIDs were tested, and it was not possible to make sensible comparisons.

Key findings

With an NSAID, initially moderate or severe cancer pain was reduced to no worse than mild pain after one or two weeks in 1 in 4 (26%) to 1 in 2 (51%) people in four studies.

Side-effect reporting was poor. Two serious side effects were reported with NSAIDs, and 22 deaths, but these were not related to pain treatment. Common side effects were thirst/dry mouth (1 in 7; 15%), loss of appetite (1 in 7; 14%), sleepiness (1 in 10; 11%), and heartburn (1 in 10; 11%). One in four people stopped taking NSAIDs because the drug did not work, and 1 in 20 stopped because of side effects.

Quality of the evidence

The quality of the evidence was very low. Very low-quality evidence means that we are very uncertain about the impact of an NSAID alone for treating cancer pain. We do not know whether using NSAIDs together with an opioid such as codeine or morphine is worthwhile.

Authors' conclusions: 

There is no high-quality evidence to support or refute the use of NSAIDs alone or in combination with opioids for the three steps of the three-step WHO cancer pain ladder. There is very low-quality evidence that some people with moderate or severe cancer pain can obtain substantial levels of benefit within one or two weeks.

Read the full abstract...
Background: 

Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Non-opioid drugs are commonly used to treat cancer pain, and are recommended for this purpose in the World Health Organization (WHO) cancer pain treatment ladder, either alone or in combination with opioids.

A previous Cochrane review that examined the evidence for nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol, alone or combined with opioids, for cancer pain was withdrawn in 2015 because it was out of date; the date of the last search was 2005. This review, and another on paracetamol, updates the evidence.

Objectives: 

To assess the efficacy of oral NSAIDs for cancer pain in adults, and the adverse events reported during their use in clinical trials.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to April 2017, together with reference lists of retrieved papers and reviews, and two online study registries.

Selection criteria: 

We included randomised, double-blind, single-blind, or open-label studies of five days' duration or longer, comparing any oral NSAID alone with placebo or another NSAID, or a combination of NSAID plus opioid with the same dose of the opioid alone, for cancer pain of any pain intensity. The minimum study size was 25 participants per treatment arm at the initial randomisation.

Data collection and analysis: 

Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.

Main results: 

Eleven studies satisfied inclusion criteria, lasting one week or longer; 949 participants with mostly moderate or severe pain were randomised initially, but fewer completed treatment or had results of treatment. Eight studies were double-blind, two single-blind, and one open-label. None had a placebo only control; eight compared different NSAIDs, three an NSAID with opioid or opioid combination, and one both. None compared an NSAID plus opioid with the same dose of opioid alone. Most studies were at high risk of bias for blinding, incomplete outcome data, or small size; none was unequivocally at low risk of bias.

It was not possible to compare NSAIDs as a group with another treatment, or one NSAID with another NSAID. Results for all NSAIDs are reported as a randomised cohort. We judged results for all outcomes as very low-quality evidence.

None of the studies reported our primary outcomes of participants with pain reduction of at least 50%, and at least 30%, from baseline; participants with Patient Global Impression of Change (PGIC) of much improved or very much improved (or equivalent wording). With NSAID, initially moderate or severe pain was reduced to no worse than mild pain after one or two weeks in four studies (415 participants in total), with a range of estimates between 26% and 51% in individual studies.

Adverse event and withdrawal reporting was inconsistent. Two serious adverse events were reported with NSAIDs, and 22 deaths, but these were not clearly related to any pain treatment. Common adverse events were thirst/dry mouth (15%), loss of appetite (14%), somnolence (11%), and dyspepsia (11%). Withdrawals were common, mostly because of lack of efficacy (24%) or adverse events (5%).

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