Clinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain. Case presentations and discussion of incomplete cross-tolerance among opioid agonist analgesics

Cancer. 1993 Oct 1;72(7):2266-72. doi: 10.1002/1097-0142(19931001)72:7<2266::aid-cncr2820720734>;2-p.


Background: Development of tolerance to opioid analgesics occurs often in patients with cancer-related pain. Cross-tolerance among opioid analgesics provides the physician with a major management problem. Incomplete cross-tolerance among opioid analgesics has been demonstrated to occur in animals and humans. The current study provides clinical evidence of the incomplete cross-tolerance of methadone with a number of mu-opioid agonist analgesics in patients with advanced cancer-related pain.

Results: Patients presented in the current study had cancer-related pain refractory to other mu--opioid receptor agonist analgesics as evidenced by inadequate analgesia despite escalation of opioid dose. All patients were adequately managed by conversion of their opioid dose to methadone. Additionally, the dose of methadone required to establish and maintain analgesia in these patients was modest compared with previous opioid dose requirements.

Conclusions: Methadone is a potent opioid analgesic that demonstrates incomplete cross-tolerance with other mu-opioid receptor agonist analgesics. Conversion of the opioid-tolerant patient with cancer-related pain to methadone may represent an important therapeutic option in the management of patients with this difficult problem.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Analgesics / pharmacology*
  • Child
  • Drug Tolerance
  • Female
  • Humans
  • Male
  • Methadone / therapeutic use*
  • Middle Aged
  • Neoplasms / physiopathology*
  • Pain, Intractable / therapy*
  • Palliative Care
  • Receptors, Opioid, mu / drug effects*


  • Analgesics
  • Receptors, Opioid, mu
  • Methadone