Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 Jul 12;7(7):CD012637.
doi: 10.1002/14651858.CD012637.pub2.

Oral paracetamol (acetaminophen) for cancer pain

Philip J Wiffen  1 , Sheena Derry, R Andrew Moore, Ewan D McNicol, Rae F Bell, Daniel B Carr, Mairead McIntyre, Bee Wee
Affiliations
Meta-Analysis

Oral paracetamol (acetaminophen) for cancer pain

Philip J Wiffen et al. Cochrane Database Syst Rev. .

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 mild to moderate cancer pain, and are recommended for this purpose in the 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for nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol, alone or combined with opioids, for cancer pain was withdrawn in 2015 because it was out of date; the date of the last search was 2005.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 NSAIDs, updates the evidence.

Objectives: To assess the efficacy of oral paracetamol (acetaminophen) for cancer pain in adults and children, and the adverse events reported during its use in clinical trials.

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

Selection criteria: We included randomised, double-blind, studies of five days' duration or longer, comparing paracetamol alone with placebo, or paracetamol in combination with an opioid compared with the same dose of the opioid alone, for cancer pain of any intensity. Single-blind and open studies were also eligible for inclusion. 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: 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.

Authors' conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

PW: none known.

SD: none known.

RAM has received grant support from Grünenthal relating to individual patient‐level analyses of trial data regarding tapentadol in osteoarthritis and back pain (2015). He has received honoraria for attending boards with Menarini concerning methods of analgesic trial design (2014), with Novartis (2014) about the design of network meta‐analyses, and RB on understanding pharmacokinetics of drug uptake (2015). He has received honoraria from Omega Pharma (2016) and Futura Pharma (2016) for providing advice on trial and data analysis methods.

EDM: none known.

RFB: none known. RFB is a specialised pain physician and has managed patients with cancer pain.

DBC: none known. DBC is a specialised pain physician and has managed patients with cancer pain.

MM: none known.

BW: none known. BW is a specialist Palliative Medicine Consultant physician and manages patients with advanced life‐threatening illnesses, including cancer.

This review was identified in a 2019 audit as not meeting the current definition of the Cochrane Commercial Sponsorship policy. At the time of its publication it was compliant with the interpretation of the existing policy. As with all reviews, new and updated, at update this review will be revised according to 2020 policy update.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012637

References

References to studies included in this review

Axelsson 2003 {published data only}
    1. Axelsson B, Borup S. Is there an additive analgesic effect of paracetamol at step 3? A double‐blind randomized controlled study. Palliative Medicine 2003;17(8):724‐5. [DOI: 10.1177/026921630301700816] - DOI - PubMed
Cubero 2010 {published data only}
    1. Cubero DI, Giglio A. Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double‐blind, placebo‐controlled study. Supportive Care in Cancer 2010;18(2):235‐42. [DOI: 10.1007/s00520-009-0649-8] - DOI - PubMed
Israel 2010 {published data only}
    1. Israel FJ, Parker G, Charles M, Reymond L. Lack of benefit from paracetamol (acetaminophen) for palliative cancer patients requiring high‐dose strong opioids: a randomized, double‐blind, placebo‐controlled, crossover trial. Journal of Pain and Symptom Management 2010;39(3):548‐54. [DOI: 10.1016/j.jpainsymman.2009.07.008] - DOI - PubMed

References to studies excluded from this review

ACTRN12610000893000 {published data only}
    1. Mitchell G (Principal Investigator). A single patient multiple cross‐over study to determine the efficacy of paracetamol in relieving pain suffered by patients with advanced cancer taking regular opioids. www.anzctr.org.au/ACTRN12610000893000.aspx (accessed 30 March 2017) 2010. [ANZCTR: ACTRN12610000893000] - PubMed
Axelsson 2008 {published data only}
    1. Axelsson B, Stellborn P, Ström G. Analgesic effect of paracetamol on cancer related pain in concurrent strong opioid therapy. A prospective clinical study. Acta Oncologica 2008;47(5):891‐5. [DOI: 10.1080/02841860701687259] - DOI - PubMed
Danninger 1993 {published data only}
    1. Danninger R, Jakse R, Beubler E. Randomized crossover‐comparison of 2 g‐ and 4 g‐doses of paracetamol per day in the case of mild to moderate pain caused by head and neck cancers. European Journal of Pain 1993;14(1):14‐8. [EMBASE: 132642 xx]
JPRN‐UMIN000009292 {published data only}
    1. Ken‐ichi Kaneko (Principle Investigator). Efficacy and safety of acetaminophen in the treatment of patients with head and neck cancer. upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000010522 (accessed 30 March 2017).
Nickles 2016 {published data only}
    1. Nickles J, Mitchell GK, Hardy J, Senior H, Carmont S‐A, Schluter PJ, et al. Single‐patient multiple crossover studies to determine the effectiveness of paracetamol in relieving pain suffered by patients with advanced cancer taking regular opioids: A pilot study. Palliative Medicine 2016;30(8):800‐2. [ANZCTR: ACTRN12609000870257; DOI: 10.1177/0269216316635012] - DOI - PubMed
Stockler 2004 {published data only}
    1. Stockler M, Vardy J, Pillai A, Warr D. Acetaminophen (paracetamol) improves pain and well‐being in people with advanced cancer already receiving a strong opioid regimen: a randomized, double‐blind, placebo‐controlled cross‐over trial. Journal of Clinical Oncology 2004;22(16):3389‐94. [DOI: 10.1200/JCO.2004.09.122] - DOI - PubMed

References to studies awaiting assessment

NCT00152854 {published data only}
    1. Vardy J (Principal Investigator). A randomised, placebo‐controlled, crossover trial of acetaminophen in cancer patients on strong opioids. clinicaltrials.gov/ct2/show/NCT00152854 (accessed 30 March 2017) 2016. [CTG: NCT00152854]
Pacilio 1989 {published data only}
    1. Pacilio G, Pizza C, Vetrano A, Mastrantoni M, Ceccarelli G. A double‐blind study on the effect of flupirtine as compared to paracetamol in the cancer pain. Riforma Medica 1989;104(1‐2):29‐32. [EMBASE: 1989176982]

References to ongoing studies

NCT02706769 {unpublished data only}
    1. University of Edinburgh. A double‐blind randomised parallel group trial of paracetamol versus placebo in conjunction with strong opioids for cancer related pain. clinicaltrials.gov/ct2/show/NCT02706769 (accessed 30 March 2017) 2016.

Additional references

AlBalawi 2013
    1. AlBalawi Z, McAlister FA, Thorlund K, Wong M, Wetterslev J. Random error in cardiovascular meta‐analyses: how common are false positive and false negative results?. Interational Journal of Cardiology 2013;168(2):1102‐7. [DOI: 10.1016/j.ijcard.2012.11.048] - DOI - PubMed
Altyar 2015
    1. Altyar A, Kordi L, Skrepnek G. Clinical and economic characteristics of emergency department visits due to acetaminophen toxicity in the USA. BMJ Open 2015;5(9):e007368. [DOI: 10.1136/bmjopen-2014-007368] - DOI - PMC - PubMed
Axelrod 2003
    1. Axelrod J. Journey of a late blooming biochemical neuroscientist. Journal of Biology and Chemistry 2003;278(1):1‐13. - PubMed
Azevedo São Leão Ferreira 2006
    1. Azevedo São Leão Ferreira K, Kimura M, Jacobsen Teixeira M. The WHO analgesic ladder for cancer pain control, twenty years of use. How much pain relief does one get from using it?. Support Care Cancer 2006;14(11):1086‐93. [DOI: 10.1016/j.critrevonc.2013.01.001] - DOI - PubMed
Bao 2016
    1. Bao YJ, Hou W, Kong XY, Yang L, Xia J, Hua BJ, et al. Hydromorphone for cancer pain. Cochrane Database of Systematic Reviews 2016, Issue 10. [DOI: 10.1002/14651858.CD011108.pub2] - DOI - PMC - PubMed
Bateman 2014a
    1. Bateman DN, Carroll R, Pettie J, Yamamoto T, Elamin ME, Peart L, et al. Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions, and costs of treatment. British Journal of Clinical Pharmacology 2014;78(3):610‐8. [DOI: 10.1111/bcp.12362] - DOI - PMC - PubMed
Bateman 2014b
    1. Bateman DN. Pack size and paracetamol overdose: 16 years later. Clinical Toxicology 2014;52:821‐3. [DOI: 10.3109/15563650.2014.952432] - DOI - PubMed
Bell 2006
    1. Bell RF, Wisløff T, Eccleston C, Kalso E. Controlled clinical trials in cancer pain. How controlled should they be? A qualitative systematic review. British Journal of Cancer 2006;94(11):1559‐67. [DOI: 10.1038/sj.bjc.6603162] - DOI - PMC - PubMed
Botting 2000
    1. Botting RM. Mechanism of action of acetaminophen: is there a cyclooxygenase 3?. Clinical Infectious Diseases 2000;31(5):S203‐10. [DOI: 10.1086/317520] - DOI - PubMed
Breivik 2009
    1. Breivik H, Cherny N, Collett B, Conno F, Filbet M, Foubert AJ, et al. Cancer‐related pain: a pan‐European survey of prevalence, treatment, and patient attitudes. Annals of Oncology 2009;20(8):1420‐33. [DOI: 10.1093/annonc/mdp001] - DOI - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta‐analyses may be inconclusive ‐ trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta‐analyses. International Journal of Epidemiology 2009;38(1):287‐98. [DOI: 10.1093/ije/dyn188] - DOI - PubMed
Brune 2015
    1. Brune K, Renner B, Tiegs G. Acetaminophen/paracetamol: a history of errors, failures and false decisions. European Journal of Pain 2015;19(7):953‐65. [10.1002/ejp.621] - PubMed
Cancer Research UK 2016
    1. Cancer statistics for the UK. www.cancerresearchuk.org/health‐professional/cancer‐statistics (accessed 21 November 2016).
Carlson 2016
    1. Carlson CL. Effectiveness of the World Health Organization cancer pain relief guidelines: an integrative review. Journal of Pain Research 2016;9:515‐34. [10.2147/JPR.S97759. eCollection 2016] - PMC - PubMed
Chandrasekharan 2002
    1. Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, et al. COX‐3, a cyclooxygenase‐1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure and expression. Proceedings of the National Academy of Sciences of the United States of America 2002;99(21):13926‐31. [DOI: 10.1073/pnas.162468699] - DOI - PMC - PubMed
Cooper 2017
    1. Cooper TE, Heathcote LC, Anderson B, Grégoire MC, Ljungman G, Eccleston C. Non‐steroidal anti‐inflammatory drugs (NSAIDs) for cancer‐related pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 2. [DOI: 10.1002/14651858.CD012563] - DOI - PMC - PubMed
CSM 1997
    1. Committee on Safety of Medicines. Medicines Control Agency. Paracetamol and aspirin. Current Problems in Pharmacovigilance 1997;23:9.
Curros‐Criado 2009
    1. Curros‐Criado MM, Herrero JF. Antinociceptive effects of NCX‐701 (nitro‐paracetamol) in neuropathic rats: enhancement of antinociception by co‐administration with gabapentin. British Journal of Pharmacology 2009;158(2):601‐9. [DOI: 10.1111/j.1476-5381.2009.00343.x] - DOI - PMC - PubMed
Dani 2007
    1. Dani M, Guindon J, Lambert C, Beaulieu P. The local antinociceptive effects of paracetamol in neuropathic pain are mediated by cannabinoid receptors. European Journal of Pharmacology 2007;573(1‐3):214‐5. [DOI: 10.1016/j.ejphar.2007.07.012] - DOI - PubMed
Dart 2000
    1. Dart RC, Kuffner EK, Rumack BH. Treatment of pain or fever with paracetamol (acetaminophen) in the alcoholic patient: a systematic review. American Journal of Medicine 2000;7(2):123‐34. [PUBMED: 11319580] - PubMed
Deandrea 2008
    1. Deandrea S, Montanari M, Moja L, Apolone G. Prevalence of undertreatment in cancer pain. A review of published literature. Annals of Oncology 2008;19(12):1985‐91. [DOI: 10.1093/annonc/mdn419] - DOI - PMC - PubMed
Dechartes 2013
    1. Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta‐epidemiological study. BMJ 2013;346:f2304. [DOI: 10.1136/bmj.f2304] - DOI - PMC - PubMed
Dechartres 2014
    1. Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association between analytic strategy and estimates of treatment outcomes in meta‐analyses. JAMA 2014;312:623‐30. [DOI: 10.1001/jama.2014.8166] - DOI - PubMed
Deng 2012
    1. Deng D, Fu L, Zhao YX, Wu X, Zhang G, Liang C, et al. The relationship between cancer pain and quality of life in patients newly admitted to Wuhan Hospice Center of China. American Journal of Hospital Palliative Care 2012;29(1):53‐9. [DOI: 10.1177/1049909111418636] - DOI - PubMed
Derry 2013
    1. Derry S, Moore RA. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD008040.pub3] - DOI - PMC - PubMed
Derry 2014
    1. Derry CJ, Derry S, Moore RA. Caffeine as an analgesic adjuvant for acute pain in adults. Cochrane Database of Systematic Reviews 2014, Issue 12. [DOI: 10.1002/14651858.CD009281.pub3] - DOI - PMC - PubMed
Derry 2017
    1. Derry S, Wiffen PJ, Moore RA, McNicol ED, Bell RF, Carr DB, et al. Oral nonsteroidal anti‐inflammatory drugs (NSAIDs) for cancer pain in adults. Cochrane Database of Systematic Reviews 2017, Issue 4. [DOI: 10.1002/14651858.CD012638] - DOI - PMC - PubMed
Dreidi 2016
    1. Dreidi MM, Hamdan‐Mansour AM. Pain, sleep disturbance, and quality of life among Palestinian patients diagnosed with cancer. Journal of Cancer Education 2016;31(4):796‐803. [DOI: 10.1007/s13187-015-0946-5] - DOI - PubMed
Drugs.com 2016
    1. Anonymous. Paracetamol. www.drugs.com/international/paracetamol.html (accessed 10 May 2016).
Dworkin 2008
    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain 2008;9(2):105‐21. [DOI: 10.1016/j.jpain.2007.09.005] - DOI - PubMed
Elbourne 2002
    1. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. - PubMed
EPOC 2015
    1. Effective Practice, Organisation of Care (EPOC). 23. Worksheets for preparing a Summary of Findings using GRADE. Resources for review authors. epoc.cochrane.org/epoc‐specific‐resources‐review‐authors (accessed 30 November 2016).
Fanelli 2017
    1. Fanelli D, Costas R, Ioannidis JP. Meta‐assessment of bias in science. Proceedings of the National Academy of Sciences of the United States of America 2017; Vol. 114, issue 14:3714‐9. [DOI: 10.1073/pnas.1618569114] - DOI - PMC - PubMed
FDA 2015
    1. Hertz S. Review of Acetaminophen for the Withdrawn or Removed List. www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drug... May 13 2015 (Accessed May 30 2017):44 et seq.
Flower 1972
    1. Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the anti‐pyretic activity of paracetamol (4‐acetamidophenol). Nature 1972;240(5381):410‐1. [PUBMED: 4564318] - PubMed
Gavaghan 2000
    1. Gavaghan DJ, Moore RA, McQuay HJ. An evaluation of homogeneity tests in meta‐analyses in pain using simulations of individual patient data. Pain 2000;85(3):415‐24. - PubMed
Graham 2005
    1. Graham GG, Scott KF. Mechanism of action of paracetamol. American Journal of Therapeutics 2005;12(1):46‐55. [DOI: 10.1097/00045391-200501000-00008] - DOI - PubMed
Gulcu 2007
    1. Gulcu N, Karaaslan K, Ozturan KE, Kocoglu H. Intravenous paracetamol for pain relief in a patient with neuropathic pain. Acta Anaesthesiologica Scandinavica 2007;51(7):956‐7. [DOI: 10.1111/j.1399-6576.2007.01362.x] - DOI - PubMed
Gulmez 2013
    1. Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jové J, et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case‐population SALT study. Drug Safety 2013;36(2):135‐44. [DOI: 10.1007/s40264-012-0013-7] - DOI - PMC - PubMed
Gulmez 2015
    1. Gulmez SE, Larrey D, Pageaux GP, Bernuau J, Bissoli F, Horsmans Y, et al. Liver transplant associated with paracetamol overdose: results from the seven‐country SALT study. British Journal of Clinical Pharmacology 2015;80(3):599‐606. [DOI: 10.1111/bcp.12635] - DOI - PMC - PubMed
Gunnell 1997
    1. Gunnell D, Hawton K, Garnier V, Bismuth C, Fagg J. Use of paracetamol for suicide and non‐fatal poisoning in the UK and France: are restrictions on availability justified?. Journal of Epidemiology and Community Health 1997;51(2):175‐9. [PUBMED: 9196648] - PMC - PubMed
Guyatt 2011
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence ‐ inconsistency. Journal of Cinical Epidemiology 2011;64(12):1294‐302. [DOI: 10.1016/j.jclinepi.2011.03.017] - DOI - PubMed
Guyatt 2013a
    1. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso‐Coello P, et al. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology 2013;66:151‐7. [DOI: 10.1016/j.jclinepi.2012.01.006] - DOI - PubMed
Guyatt 2013b
    1. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables ‐ binary outcomes. Journal of Clinical Epidemiology 2013;66:158‐72. [DOI: 10.1016/j.jclinepi.2012.01.012] - DOI - PubMed
Hadley 2013
    1. Hadley G, Derry S, Moore RA, Wiffen PJ. Transdermal fentanyl for cancer pain. Cochrane Database of Systematic Reviews 2013, Issue 10. [DOI: 10.1002/14651858.CD010270.pub2] - DOI - PMC - PubMed
Hawkins 2007
    1. Hawkins LC, Edwards JN, Dargan PI. Impact of restricting paracetamol pack sizes on paracetamol poisoning in the United Kingdom: a review of the literature. Drug Safety 2007;30(6):465‐79. [PUBMED: 17536874] - PubMed
Hawton 2001
    1. Hawton K, Townsend E, Deeks J, Appleby L, Gunnell D, Bennewith O, et al. Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study. BMJ 2001;322(7296):1203‐7. [DOI: 10.1136/bmj.322.7296.1203] - DOI - PMC - PubMed
Hawton 2013
    1. Hawton K, Bergen H, Simkin S, Dodd S, Pocock P, Bernal W, et al. Long term effect of reduced pack sizes of paracetamol on poisoning deaths and liver transplant activity in England and Wales: interrupted time series analyses. BMJ 2013;346:f403. [DOI: 10.1136/bmj.f403] - DOI - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hinz 2008
    1. Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase‐2 inhibitor in man. Federation of American Societies for Experimental Biology Journal 2008;22(2):383‐90. [DOI: 10.1096/fj.07-8506com] - DOI - PubMed
IARC 2012
    1. International Agency for Research on Cancer. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. globocan.iarc.fr/Pages/fact_sheets_cancer.aspx (accessed 21 November 2016).
IntHout 2015
    1. IntHout J, Ioannidis JP, Borm GF, Goeman JJ. Small studies are more heterogeneous than large ones: a meta‐meta‐analysis. Journal of Clinical Epidemiology 2015;68:860‐9. [DOI: 10.1016/j.jclinepi.2015.03.017] - DOI - PubMed
Jadad 1995
    1. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of Its evaluation. JAMA 1995;274(23):1870‐3. - PubMed
Liew 2014
    1. Liew Z, Ritz B, Rebordosa C, Lee PC, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatrics 2014;168(4):313‐20. [DOI: 10.1001/jamapediatrics.2013.4914] - DOI - PubMed
Machado 2015
    1. Machado GC, Maher CG, Ferreira PH, Pinheiro MB, Lin CW, Day RO, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta‐analysis of randomised placebo controlled trials. BMJ 2015;350:h1225. [DOI: 10.1136/bmj.h1225] - DOI - PMC - PubMed
Mazaud‐Guittot 2013
    1. Mazaud‐Guittot S, Nicolas Nicolaz C, Desdoits‐Lethimonier C, Coiffec I, Ben Maamar M, Balaguer P, et al. Paracetamol, aspirin, and indomethacin induce endocrine disturbances in the human fetal testis capable of interfering with testicular descent. Journal of Clinical Endocrinology and Metabolism 2013;98(11):1757‐67. [DOI: 10.1210/jc.2013-2531] - DOI - PubMed
McQuay 1998
    1. McQuay H, Moore A. An Evidence‐based Resource for Pain Relief. Oxford: Oxford University Press, 1998. [ISBN: 0‐19‐263048‐2]
McQuay 2005
    1. McQuay HJ, Moore RA. Placebo. Postgraduate Medical Journal 2005;81(953):155‐60. - PMC - PubMed
McQuay 2007
    1. McQuay HJ, Moore RA. Dose‐response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies. British Journal of Clinical Pharmacology 2007;63(3):271‐8. - PMC - PubMed
Mercadante 2013
    1. Mercadante S, Giarratano A. The long and winding road of nonsteroidal anti‐inflammatory drugs and paracetamol in cancer pain management: a critical review. Critical Reviews in Oncology/Hematology 2013;87:140‐5. [DOI: 10.1016/j.critrevonc.2013.01.001] - DOI - PubMed
Mercadante 2014
    1. Mercadante S, Giarratano A. Pharmacological management of cancer pain in children. Clinical Reviews in Oncology and Hematology 2014;91(1):93‐7. [DOI: 10.1016/j.critrevonc.2014.01.005] - DOI - PubMed
Mikan 2016
    1. Mikan F, Wada M, Yamada M, Takahashi A, Onishi H, Ishida M, et al. The association between pain and quality of life for patients with cancer in an outpatient clinic, an inpatient oncology ward, and inpatient palliative care units. American Journal of Hospital Palliative Care 2016;33(8):782‐90. [DOI: 10.1177/1049909116630266] - DOI - PubMed
Moore 1998
    1. Moore RA, Gavaghan D, Tramèr MR, Collins SL, McQuay HJ. Size is everything ‐ large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78(3):209‐16. [DOI: 10.1016/S0304-3959(98)00140-7] - DOI - PubMed
Moore 2008
    1. Moore RA, Barden J, Derry S, McQuay HJ. Managing potential publication bias. In: McQuay HJ, Kalso E, Moore RA editor(s). Systematic Reviews in Pain Research: Methodology Refined. Seattle: IASP Press, 2008:15‐24. [ISBN: 978–0–931092–69–5]
Moore 2010a
    1. Moore RA, Moore OA, Derry S, Peloso PM, Gammaitoni AR, Wang H. Responder analysis for pain relief and numbers needed to treat in a meta‐analysis of etoricoxib osteoarthritis trials: bridging a gap between clinical trials and clinical practice. Annals of the Rheumatic Diseases 2010;69(2):374‐9. [DOI: 10.1136/ard.2009.107805] - DOI - PMC - PubMed
Moore 2010b
    1. Moore RA, Derry S, McQuay HJ, Straube S, Aldington D, Wiffen P, et al. Clinical effectiveness: an approach to clinical trial design more relevant to clinical practice, acknowledging the importance of individual differences. Pain 2010;149(2):173‐6. [DOI: 10.1016/j.pain.2009.08.007] - DOI - PubMed
Moore 2013a
    1. Moore RA, Straube S, Aldington D. Pain measures and cut‐offs ‐ 'no worse than mild pain' as a simple, universal outcome. Anaesthesia 2013;68(4):400‐12. [DOI: 10.1111/anae.12148] - DOI - PubMed
Moore 2013b
    1. Moore RA. What works for whom? Determining the efficacy and harm of treatments for pain. Pain 2013;154 Suppl 1:S77‐86. [DOI: 10.1016/j.pain.2013.03.024] - DOI - PubMed
Moore 2014
    1. Moore RA, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non‐cancer pain and chronic neuropathic pain. Pain Practice 2014;14(1):79‐94. [DOI: 10.1111/papr.12050] - DOI - PubMed
Moore 2014a
    1. Moore RA, Derry S, Wiffen PJ, Straube S, Aldington DJ. Overview review: comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions. European Journal of Pain 2014;19(9):1213‐23. [DOI: 10.1002/ejp.649] - DOI - PubMed
Moore 2016
    1. Moore RA, Moore N. Paracetamol and pain: the kiloton problem. European Journal of Hospital Pharmacy 2016;23(4):187‐8. [DOI: 10.1136/ejhpharm-2016-000952] - DOI - PMC - PubMed
Nabal 2012
    1. Nabal M, Librada S, Redondo MJ, Pigni A, Brunelli C, Caraceni A. The role of paracetamol and nonsteroidal anti‐inflammatory drugs in addition to WHO Step III opioids in the control of pain in advanced cancer. A systematic review of the literature. Palliative Medicine 2012;26(4):305‐12. [DOI: 10.1177/0269216311428528] - DOI - PubMed
Nguyen 2017
    1. Nguyen TL, Collins GS, Lamy A, Devereaux PJ, Daurès JP, Landais P, et al. Simple randomization did not protect against bias in smaller trials. Journal of Clinical Epidemiology 2017;84:105‐13. [DOI: 10.1016/j.jclinepi.2017.02.010] - DOI - PubMed
NICE 2016
    1. National Institute for Health and Care Excellence. Palliative cancer care ‐ pain. cks.nice.org.uk/palliative‐cancer‐care‐pain (accessed 02 February 2017).
Norris 2008
    1. Norris W, Paredes AH, Lewis JH. Drug‐induced liver injury in 2007. Current Opinion in Gastroenterology 2008;24(3):287‐97. [DOI: 10.1097/MOG.0b013e3282f9764b] - DOI - PubMed
Nüesch 2010
    1. Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta‐analyses of osteoarthritis trials: meta‐epidemiological study. BMJ 2010;341:c3515. [DOI: 10.1136/bmj.c3515] - DOI - PMC - PubMed
PaPaS 2012
    1. Cochrane Pain, Palliative and Supportive Care Group. PaPaS author and referee guidance. papas.cochrane.org/papas‐documents (accessed 21 November 2016).
PIC 2015
    1. PharmWeb. Paracetamol Information Centre. www2.pharmweb.net/pwmirror/pwy/paracetamol/pharmwebpic.html (accessed 18 January 2016).
Portenoy 1999
    1. Portenoy RK, Lesage P. Management of cancer pain. Lancet 1999;353(9165):1695‐700. [DOI: 10.1016/S0140-6736(99)01310-0] - DOI - PubMed
Prescott 2000
    1. Prescott LF. Therapeutic misadventure with paracetamol: fact or fiction?. American Journal of Therapeutics 2000;7(2):99‐114. [PUBMED: 11319578] - PubMed
Prommer 2015
    1. Prommer EE. Pharmacological management of cancer‐related pain. Cancer Control 2015;22(4):412‐25. [PUBMED: 26678968] - PubMed
RevMan 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Roberts 2015
    1. Roberts I, Ker K, Edwards P, Beecher D, Manno D, Sydenham E. The knowledge system underpinning healthcare is not fit for purpose and must change. BMJ 2015;350:h2463. [DOI: 10.1136/bmj.h2463] - DOI - PubMed
Roberts 2016
    1. Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M, Miller P, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Annals of the Rheumatic Diseases 2016;75(3):552‐9. [DOI: 10.1136/annrheumdis-2014-206914] - DOI - PMC - PubMed
Saragiotto 2016
    1. Saragiotto BT, Machado GC, Ferreira ML, Pinheiro MB, Abdel Shaheed C, Maher CG. Paracetamol for low back pain. Cochrane Database of Systematic Reviews 2016, Issue 6. [DOI: 10.1002/14651858.CD012230] - DOI - PMC - PubMed
Schmidt‐Hansen 2015a
    1. Schmidt‐Hansen M, Bromham N, Taubert M, Arnold S, Hilgart JS. Buprenorphine for treating cancer pain. Cochrane Database of Systematic Reviews 2015, Issue 3. [DOI: 10.1002/14651858.CD009596.pub4] - DOI - PMC - PubMed
Schmidt‐Hansen 2015b
    1. Schmidt‐Hansen M, Bennett MI, Arnold S, Bromham N, Hilgart JS. Oxycodone for cancer‐related pain. Cochrane Database of Systematic Reviews 2015, Issue 2. [DOI: 10.1002/14651858.CD003870.pub5] - DOI - PubMed
Schwab 2003
    1. Schwab JM, Schluesener HJ, Laufer S. COX‐3: just another COX or the solitary elusive target of paracetamol?. Lancet 2003;361(9362):981‐2. [DOI: 10.1016/S0140-6736(03)12841-3] - DOI - PubMed
Straube 2014
    1. Straube C, Derry S, Jackson KC, Wiffen PJ, Bell RF, Strassels S, et al. Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database of Systematic Reviews 2014, Issue 9. [DOI: 10.1002/14651858.CD006601.pub4] - DOI - PMC - PubMed
Thorlund 2011
    1. Thorlund K, Imberger G, Walsh M, Chu R, Gluud C, Wetterslev J, et al. The number of patients and events required to limit the risk of overestimation of intervention effects in meta‐analysis ‐ a simulation study. PLOS One 2011;6(10):e25491. [DOI: 10.1371/journal.pone.0025491] - DOI - PMC - PubMed
Toms 2008
    1. Toms L, McQuay HJ, Derry S, Moore RA. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD004602.pub2] - DOI - PMC - PubMed
Turner 2013
    1. Turner RM, Bird SM, Higgins JP. The impact of study size on meta‐analyses: examination of underpowered studies in Cochrane reviews. PLOS One 2013;8(3):e59202. [DOI: 10.1371/journal.pone.0059202] - DOI - PMC - PubMed
Twycross 2014
    1. Twycross R, Wilcock A, Howard P. Palliative Care Formulary. Nottingham: Palliativedrugs.com Ltd, 2014.
Twycross 2015
    1. Twycross A, Parker R, Williams A, Gibson F. Cancer‐related pain and pain management: sources, prevalence, and the experiences of children and parents. Journal of Paediatric Oncology Nursing 2015;32(6):369‐84. [DOI: 10.1177/1043454214563751] - DOI - PubMed
Van den Beuken‐van Everdingen 2016
    1. Beuken‐van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan‐Heijnen VC, Janssen DJ. Update on prevalence of pain in patients with cancer: systematic review and meta‐analysis. Journal of Pain and Symptom Management 2016;51:1070‐90. [DOI: 10.1016/j.jpainsymman.2015.12.340] - DOI - PubMed
Ventafridda 1990
    1. Ventafridda V, Conno F, Panerai AE, Maresca V, Monza GC, Ripamonti C. Non‐steroidal anti‐inflammatory drugs as the first step in cancer pain therapy: double‐blind, within‐patient study comparing nine drugs. Journal of International Medical Research 1990;18(1):21‐9. [DOI: 10.1177/030006059001800104] - DOI - PubMed
WHO 2017
    1. Anonymous. WHO analgesic ladder. www.who.int/cancer/palliative/painladder/en/ (accessed 10 April 2017).
Wiffen 2014
    1. Wiffen PJ, Derry S, Moore RA. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain. Cochrane Database of Systematic Reviews 2014, Issue 5. [DOI: 10.1002/14651858.CD011056.pub2] - DOI - PMC - PubMed
Wiffen 2015
    1. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD011460.pub2] - DOI - PMC - PubMed
Wiffen 2016
    1. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database of Systematic Reviews 2016, Issue 4. [DOI: 10.1002/14651858.CD003868.pub4] - DOI - PMC - PubMed
Wiffen 2017
    1. Wiffen PJ, Derry S, Moore RA. Tramadol with or without paracetamol (acetaminophen) for cancer pain. Cochrane Database of Systematic Reviews 2017, Issue 1. [DOI: 10.1002/14651858.CD012508] - DOI - PMC - PubMed
Williams 2014
    1. Williams CM, Maher CG, Latimer J, McLachlan AJ, Hancock MJ, Day RO, et al. Efficacy of paracetamol for acute low‐back pain: a double‐blind, randomised controlled trial. Lancet 2014;384(9954):1586‐96. [DOI: 10.1016/S0140-6736(14)60805-9] - DOI - PubMed
Zhao 2011
    1. Zhao L, Pickering G. Paracetamol metabolism and related genetic differences. Drug Metabolism Reviews 2011;43(1):41‐52. [DOI: 10.3109/03602532.2010.527984] - DOI - PubMed

References to other published versions of this review

McNicol 2015
    1. McNicol ED, Strassels S, Goudas L, Lau J, Carr DB. NSAIDS or paracetamol, alone or combined with opioids, for cancer pain. Cochrane Database of Systematic Reviews 2015, Issue 7. [DOI: 10.1002/14651858.CD005180.pub2] - DOI - PMC - PubMed
wife 2017b
    1. Wiffen PJ, Derry S, Moore RA, McNicol ED, Bell RF, Carr DB, et al. Oral paracetamol (acetaminophen) for cancer pain. Cochrane Database of Systematic Reviews 2017, Issue 4. [DOI: 10.1002/14651858.CD012637] - DOI - PMC - PubMed

Publication types

MeSH terms