Abstract: Three studies in adults satisfied the inclusion criteria, lasting up to one week; 122 participants were randomised initially, and 95 completed treatment. We found no studies in children. One study was parallel-group, and two had a cross-over design. All used paracetamol as an add-on to established treatment with strong opioids (median daily morphine equivalent doses of 60 mg, 70 mg, and 225 mg, with some participants taking several hundred mg of oral morphine equivalents daily). Other non-paracetamol medication included non-steroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, or neuroleptics. All studies were at high risk of bias for incomplete outcome data and small size; none was unequivocally at low risk of bias. None of the studies reported any of our primary outcomes: participants with pain reduction of at least 50%, and at least 30%, from baseline; participants with pain no worse than mild at the end of the treatment period; participants with Patient Global Impression of Change (PGIC) of much improved or very much improved (or equivalent wording). What pain reports there were indicated no difference between paracetamol and placebo when added to another treatment. There was no convincing evidence of paracetamol being different from placebo with regards to quality of life, use of rescue medication, or participant satisfaction or preference. Measures of harm (serious adverse events, other adverse events, and withdrawal due to lack of efficacy) were inconsistently reported and provided no clear evidence of difference. Our GRADE assessment of evidence quality was very low for all outcomes, because studies were at high risk of bias from several sources. There is no high-quality evidence to support or refute the use of paracetamol alone or in combination with opioids for the first two steps of the three-step WHO cancer pain ladder. It is not clear whether any additional analgesic benefit of paracetamol could be detected in the available studies, in view of the doses of opioids used.

Plain-language summary: In this review we set out to examine all the evidence on how well paracetamol (alone or with morphine-like drugs) worked in adults and children with cancer pain. We also wanted to know how many people had side effects, and how severe those side effects were, for example, whether they caused people to stop taking their medicines. In March 2017, we found three studies with 122 participants. All compared paracetamol plus opioid with the same dose of opioid alone. The studies were small, and were of poor quality. They used different study designs and different ways of showing their pain results. Outcomes of importance to people with cancer pain were not reported. We found no evidence that taking paracetamol alone made any difference to the level of pain experienced. We found no evidence that taking paracetamol together with a morphine-like drug was better than the morphine-like drug alone. Paracetamol did not appear to improve quality of life. No conclusions could be reached about side effects. The amount of information and the differences in how studies were reported meant that no conclusions could be made. The quality of the evidence was very low. Very low-quality evidence means that we are very uncertain about the impact of paracetamol for treating cancer pain. We do not know whether using paracetamol alone, or in combination with an opioid such as codeine or morphine, is worthwhile.