Supportive Care in Cancer

, Volume 13, Issue 3, pp 138–144 | Cite as

Advances in opioid therapy and formulations

  • Declan WalshEmail author
Review Article


Newly developed opioid analgesics and drug delivery systems may provide pain relief for patients intolerant of morphine. Long-acting oral opioids supply satisfactory analgesia at more convenient dosing intervals. Implantable pumps can provide full analgesic doses of opioids both subcutaneously and intrathecally over extended time periods. Optimal opioid use should rely on individualized dose-finding approaches to enhance pain relief while limiting drug-related side effects and avoiding the common problems associated with opioid prescription in clinical practice.


Opioids Formulations Drug delivery systems Dosing strategies 



This manuscript was supported by Endo Pharmaceuticals, Chadds Ford, PA, USA, with editorial assistance provided by Accel Medical Education, New York, NY, USA.


  1. 1.
    Daut RL, Cleeland CS (1982) The prevalence and severity of pain in cancer. Cancer 50:1913–1918Google Scholar
  2. 2.
    Expert Working Group of the European Association for Palliative Care (1996) Morphine in cancer pain: modes of administration. BMJ 312:823–826Google Scholar
  3. 3.
    Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, Mercadante S, Pasternak G, Ventafridda V (2001) Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol 19:2542–2554Google Scholar
  4. 4.
    Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, Mercadante S, Meynadier J, Poulain P, Ripamonti C, Radbruch L, Casas JR, Sawe J, Twycross RG, Ventafridda V (2001) Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 84:587–593CrossRefGoogle Scholar
  5. 5.
    Bruera E, Belzile M, Pituskin E, Faisinger R, Darke A, Harsanyi Z, Babul N, Ford I (1998) Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. J Clin Oncol 16:3222–3229Google Scholar
  6. 6.
    Galer BS, Coyle N, Pasternak GW, Portenoy RK (1992) Individual variability in the response to different opioids: report of five cases. Pain 49:87–91CrossRefGoogle Scholar
  7. 7.
    Ripamonti C, Dickerson ED (2001) Strategies for the treatment of cancer pain in the new millennium. Drugs 61:955–977Google Scholar
  8. 8.
    de Stoutz ND, Bruera E, Suarez-Almazor M (1995) Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage 10:378–384Google Scholar
  9. 9.
    Gourlay GK, Cherry DA, Cousins MJ (1986) A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Pain 25:297–312CrossRefGoogle Scholar
  10. 10.
    Warfield CA (1998) Controlled-release morphine tablets in patients with chronic cancer pain: a narrative review of controlled clinical trials. Cancer 82:2299–2306CrossRefGoogle Scholar
  11. 11.
    Hanks GW (1989) Controlled-release morphine (MST Contin) in advanced cancer. The European experience. Cancer 63:2378–2382Google Scholar
  12. 12.
    Cundiff D, McCarthy K, Savarese JJ, Kaiko R, Thomas G, Grandy R, Goldenheim P (1989) Evaluation of a cancer pain model for the testing of long-acting analgesics. The effect of MS Contin in a double-blind, randomized crossover design. Cancer 63:2355–2359Google Scholar
  13. 13.
    Broomhead A, Kerr R, Tester W, O’Meara P, Maccarrone C, Bowles R, Hodsman P(1997) Comparison of a once-a-day sustained-release morphine formulation with standard oral morphine treatment for cancer pain. J Pain Symptom Manage 14:63–73CrossRefGoogle Scholar
  14. 14.
    Davis MP, Varga J, Dickerson D, Walsh D, LeGrand SB, Lagman R (2003) Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy. Support Care Cancer 11:84–92Google Scholar
  15. 15.
    Gimbel JS, Richards P, Portenoy RK (2003) Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology 60:927–934Google Scholar
  16. 16.
    Watson CP, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J (2003) Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain 105:71–78CrossRefGoogle Scholar
  17. 17.
    Roth SH, Fleischmann RM, Burch FX, Dietz F, Bockow B, Rapoport RJ, Rutstein J, Lacouture PG (2000) Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Arch Intern Med 160:853–860CrossRefGoogle Scholar
  18. 18.
    Cheville A, Chen A, Oster G, McGarry L, Narcessian E (2001) A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty. J Bone Joint Surg Am 83-A:572–576Google Scholar
  19. 19.
    Heiskanen T, Kalso E (1997) Controlled-release oxycodone and morphine in cancer related pain. Pain 73:37–45CrossRefGoogle Scholar
  20. 20.
    Mucci-LoRusso P, Berman BS, Silberstein PT, Citron ML, Bressler L, Weinstein SM, Kaiko RF, Buckley BJ, Reder RF (1998) Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study. Eur J Pain 2:239–249PubMedGoogle Scholar
  21. 21.
    Davis MP (2003) Equianalgesia – paradox and pitfalls. J Terminal Oncol 2:89–91Google Scholar
  22. 22.
    Payne R (1998) Factors influencing quality of life in cancer patients: the role of transdermal fentanyl in the management of pain. Semin Oncol 25:47–53Google Scholar
  23. 23.
    Allan L, Hays H, Jensen NH, de Waroux BL, Bolt M, Donald R, Kalso E (2001) Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 322:1154–1158CrossRefGoogle Scholar
  24. 24.
    Sloan PA, Moulin DE, Hays H (1998) A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain. J Pain Symptom Manage 16:102–111CrossRefGoogle Scholar
  25. 25.
    Mystakidou K, Befon S, Tsilika E, Dardoufas K, Georgaki S, Vlahos L (2002) Use of TTS fentanyl as a single opioid for cancer pain relief: a safety and efficacy clinical trial in patients naive to mild or strong opioids. Oncology 62:9–16CrossRefGoogle Scholar
  26. 26.
    Wong JO, Chiu GL, Tsao CJ, Chang CL (1997) Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain. Acta Anaesthesiol Sin 35:25–32Google Scholar
  27. 27.
    Beaver WT, Wallenstein SL, Houde RW, Rogers A (1977) Comparisons of the analgesic effects of oral and intramuscular oxymorphone and of intramuscular oxymorphone and morphine in patients with cancer. J Clin Pharmacol 17:186–198Google Scholar
  28. 28.
    Gabrail NY, Dvergsten C, Ma T, Frailey A, Ahdieh H (2003) Oxymorphone extended release (ER) in opioid rotation. Presented at the 15th MASCC International Symposium; June 18–21, 2003; Berlin, Germany [A-36]. Support Care Cancer 11:396Google Scholar
  29. 29.
    Sloan P (2002) Analgesic safety and efficacy of extended release oxymorphone for the treatment of cancer pain. Support Care Cancer 10:360Google Scholar
  30. 30.
    Sinatra RS, Lodge K, Sibert K, Chung KS, Chung JH, Parker A, Jr, Harrison DM (1989) A comparison of morphine, meperidine, and oxymorphone as utilized in patient-controlled analgesia following cesarean delivery. Anesthesiology 10:585–590Google Scholar
  31. 31.
    Inturrisi CE (2002) Clinical pharmacology of opioids for pain. Clin J Pain 18:S3–13CrossRefGoogle Scholar
  32. 32.
    Endo/Penwest (2003) Oxymorphone—EN 3202, EN 3203. Drugs R D 4:204–206Google Scholar
  33. 33.
    McIlwain H, Burch F, Frailey A, Ma T, Ahdieh H (2003) Oxymorphone extended-release offers long-term safety, effectiveness, and dose stabilization in osteoarthritis pain: results of a one-year interim report. Presented at the American Pain Society 22nd Annual Scientific Meeting; March 20–23, 2003; Chicago, IL [poster 908] Google Scholar
  34. 34.
    Slatkin N (2003) Long-term safety, efficacy, and dose stabilization of oxymorphone ER in cancer pain. Support Care Cancer 11:397Google Scholar
  35. 35.
    Durect Corporation (2001) DUROS technology platform. Fact sheet. Cupertino, CAGoogle Scholar
  36. 36.
    Howell SB (2001) Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology. Cancer J 7:219–227Google Scholar
  37. 37.
    Yaksh TL, Provencher JC, Rathbun ML, Myers RR, Powell H, Richter P, Kohn FR (2000) Safety assessment of encapsulated morphine delivered epidurally in a sustained-release multivesicular liposome preparation in dogs. Drug Deliv 7:27–36Google Scholar
  38. 38.
    Crews JC (1990) Epidural opioid analgesia. Crit Care Clin 6:315–342Google Scholar
  39. 39.
    Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, Buchser E, Català E, Bryce DA, Coyne PJ, Pool GE (2002) Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol 20:4040–4049CrossRefGoogle Scholar
  40. 40.
    Wright PM, O’Toole DP, Barron DW (1992) The influence of naloxone infusion on the action of intrathecal diamorphine: low-dose naloxone and neuroendocrine responses. Acta Anaesthesiol Scand 36:230–233Google Scholar
  41. 41.
    Joshi GP, Duffy L, Chehade J, Wesevich J, Gajraj N, Johnson ER (1999) Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. Anesthesiology 90:1007–1011CrossRefGoogle Scholar
  42. 42.
    Donnelly S, Davis MP, Walsh D, Naughton M (2002) Morphine in cancer pain management: a practical guide. Support Care Cancer 10:13–35CrossRefGoogle Scholar
  43. 43.
    Seeman P (2002) Atypical antipsychotics: mechanism of action. Can J Psychiatry 47:27–38Google Scholar
  44. 44.
    Kochhar R, LeGrand SB, Walsh D, Davis MP, Lagman R, Rivera NI (2003) Opioids in cancer pain: common dosing errors. Oncology 17:571–575Google Scholar
  45. 45.
    Walsh D (2000) Pharmacological management of cancer pain. Semin Oncol 27:45–63Google Scholar
  46. 46.
    Brant JM (2001) Opioid equianalgesic conversion: the right dose. Clin J Oncol Nurs 5:163–165Google Scholar
  47. 47.
    Blumstein HA, Moore D (2003) Visual analog pain scores do not define desire for analgesia in patients with acute pain. Acad Emerg Med 10:211–214CrossRefGoogle Scholar
  48. 48.
    Reyes-Gibby CC, McCrory LL, Cleeland CS (2003) Variations in patients’ self-report of pain by treatment setting. J Pain Symptom Manage 25:444–448CrossRefGoogle Scholar
  49. 49.
    Walsh D, Rivera NI, Davis MP, Lagman R, LeGrand SB (2004) Strategies for pain managment: Cleveland Clinic Foundation Guidelines for opioid dosing for cancer pain. Support Care Cancer 1:157–164Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.The Harry R. Horvitz Center for Palliative MedicineThe Cleveland Clinic Taussig Cancer CenterClevelandUSA
  2. 2.The Cleveland Clinic FoundationClevelandUSA

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