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Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults.
Cochrane Database Syst Rev 2017; 7:CD012638CD

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for nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol, alone or combined with opioids, for cancer pain was withdrawn in 2015 because it was out of date; the date of the last search was 2005.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 METHODS

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%).

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.

Authors+Show Affiliations

Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

28700091

Citation

Derry, Sheena, et al. "Oral Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Cancer Pain in Adults." The Cochrane Database of Systematic Reviews, vol. 7, 2017, p. CD012638.
Derry S, Wiffen PJ, Moore RA, et al. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults. Cochrane Database Syst Rev. 2017;7:CD012638.
Derry, S., Wiffen, P. J., Moore, R. A., McNicol, E. D., Bell, R. F., Carr, D. B., ... Wee, B. (2017). Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults. The Cochrane Database of Systematic Reviews, 7, p. CD012638. doi:10.1002/14651858.CD012638.pub2.
Derry S, et al. Oral Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Cancer Pain in Adults. Cochrane Database Syst Rev. 2017 07 12;7:CD012638. PubMed PMID: 28700091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults. AU - Derry,Sheena, AU - Wiffen,Philip J, AU - Moore,R Andrew, AU - McNicol,Ewan D, AU - Bell,Rae F, AU - Carr,Daniel B, AU - McIntyre,Mairead, AU - Wee,Bee, Y1 - 2017/07/12/ PY - 2017/7/13/pubmed PY - 2017/9/12/medline PY - 2017/7/13/entrez SP - CD012638 EP - CD012638 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev VL - 7 N2 - 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 METHODS: 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%). 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/28700091/Oral_nonsteroidal_anti_inflammatory_drugs__NSAIDs__for_cancer_pain_in_adults_ L2 - https://doi.org/10.1002/14651858.CD012638.pub2 DB - PRIME DP - Unbound Medicine ER -