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

Palliat Med. 2012 Jun;26(4):305-12. doi: 10.1177/0269216311428528. Epub 2011 Nov 29.


Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are used widely in the management of mild to moderate cancer pain and are frequently combined with opioids in the treatment of moderate to severe pain.

Aim: To perform a systematic literature review of the evidence of the efficacy and toxicity of NSAIDs or paracetamol added to WHO Step III opioid treatment for cancer pain.

Design and data sources: A systematic literature review of MedLine, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms.

Results: Seven eligible papers were retrieved from the new search and five from the Cochrane review. Five of seven studies showed an additive effect of NSAIDs when combined with opioids either by improving analgesia (three studies) or by reducing the opioid dose (two studies). Paracetamol was only marginally effective in one of five trials. The study designs were not adequate to assess differences in side effects between the opioids alone and opioids in combination with NSAIDs or paracetamol.

Conclusions: The evidence from the available clinical trials is of limited amount and quality, but it weakly supports the proposal that the addition of an NSAIDs to WHO Step III opioids can improve analgesia or reduce opioid dose requirement. There is insufficient evidence to support the use of paracetamol in combination with Step III opioids. Data on the toxicity of NSAIDs in this indication are insufficient owing to the small number of patients and the short duration of treatment reported in the studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Acetaminophen / therapeutic use*
  • Analgesics, Non-Narcotic / therapeutic use*
  • Analgesics, Opioid / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination / methods
  • Humans
  • Neoplasms / complications*
  • Neoplasms / pathology
  • Pain / drug therapy*
  • Pain / etiology


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen