Abstract: 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%). 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.

Plain-language summary: 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. 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. 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.