Pharmacological options for the management of refractory cancer pain-what is the evidence?

Support Care Cancer. 2015 May;23(5):1473-81. doi: 10.1007/s00520-015-2678-9. Epub 2015 Mar 7.


Refractory cancer pain that does not respond to standard opioid and/or co-analgesic therapy occurs in 10-20 % of patients. Risk factors include young age, neuropathic pain type, incident pain, psychological distress, previous opioid use, high tolerance, a history of addiction and impaired cognition. The management of patients with refractory pain remains a challenge. Treatment options include opioid manipulation (parenteral delivery, rotation, combination, methadone and buprenorphine), non-opioids and co-analgesics (paracetamol, non-steroidal anti-inflammatory agents, antidepressants and anticonvulsants), NMDA receptor antagonists, cannabinoids, lignocaine and corticosteroids. The evidence of benefit for any of these agents is weak, and each additional agent increases the risk of adverse events. Evidence-based guidelines cannot, therefore, be developed at present. New approaches are recommended including targeted opioid therapy, multimodal analgesia, a goal-oriented approach to pain management and increasing use of the multidisciplinary team and support services.

Publication types

  • Review

MeSH terms

  • Acetaminophen / therapeutic use
  • Analgesics, Opioid / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antidepressive Agents / therapeutic use
  • Buprenorphine / therapeutic use
  • Drug Therapy, Combination
  • Drug Tolerance
  • Humans
  • Methadone / therapeutic use
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Pain Management / methods*
  • Pain, Intractable / drug therapy*
  • Pain, Intractable / etiology*


  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antidepressive Agents
  • Acetaminophen
  • Buprenorphine
  • Methadone