UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Cancer pain management with opioids: Optimizing analgesia

Authors
Russell K Portenoy, MD
Zankhana Mehta, MD
Ebtesam Ahmed, PharmD, MS
Section Editor
Janet Abrahm, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Opioids are widely used for treatment of pain in patients with cancer because of their safety, multiple routes of administration, ease of titration, reliability, and effectiveness for all types of pain (ie, somatic, visceral, neuropathic). Although neuropathic pain may be more difficult to treat, a favorable response to opioid-based analgesia is often possible. (See "Assessment of cancer pain", section on 'Inferred pathophysiology (types of cancer pain)'.)

Opioids are also potentially abusable drugs. The public health consequences of opioid abuse drive the imperative that all physicians assume responsibility for risk management when these drugs are prescribed for legitimate medical purposes. These issues are discussed elsewhere. (See "Cancer pain management: General principles and risk management for patients receiving opioids", section on 'Risk assessment and management for patients receiving opioids'.)

This topic review will cover the use of opioids for cancer-related pain, with an emphasis on optimizing analgesia and minimizing side effects. Assessment of cancer pain, a review of specific cancer pain syndromes, general principles of cancer pain management, an overview of risk management in patients treated with opioids, prevention and management of opioid side effects, the clinical use of non-opioid analgesics (including NSAIDs and adjuvant analgesics), non-pharmacologic methods of cancer pain management, management of acute pain (eg, from a new injury or surgical procedure) in the patient chronically using opioids, and issues surrounding pain management in the last weeks of life are covered elsewhere.

(See "Assessment of cancer pain".)

(See "Overview of cancer pain syndromes".)

                                      

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Fri Nov 11 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Mercadante S, Porzio G, Ferrera P, et al. Low doses of transdermal buprenorphine in opioid-naive patients with cancer pain: a 4-week, nonrandomized, open-label, uncontrolled observational study. Clin Ther 2009; 31:2134.
  2. Apolone G, Corli O, Negri E, et al. Effects of transdermal buprenorphine on patients-reported outcomes in cancer patients: results from the Cancer Pain Outcome Research (CPOR) Study Group. Clin J Pain 2009; 25:671.
  3. Poulain P, Denier W, Douma J, et al. Efficacy and safety of transdermal buprenorphine: a randomized, placebo-controlled trial in 289 patients with severe cancer pain. J Pain Symptom Manage 2008; 36:117.
  4. Sittl R. Transdermal buprenorphine in cancer pain and palliative care. Palliat Med 2006; 20 Suppl 1:s25.
  5. Sittl R, Griessinger N, Likar R. Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: a multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther 2003; 25:150.
  6. Sarhan T, Doghem M.. A cmparison of two transdermal drug delivery systems; buprenorphine and fentanyl for chronic pain management. Eur J Pain 2009; 13:S199.
  7. Pace MC, Passavanti MB, Grella E, et al. Buprenorphine in long-term control of chronic pain in cancer patients. Front Biosci 2007; 12:1291.
  8. Pergolizzi JV Jr, Mercadante S, Echaburu AV, et al. The role of transdermal buprenorphine in the treatment of cancer pain: an expert panel consensus. Curr Med Res Opin 2009; 25:1517.
  9. Schmidt-Hansen M, Taubert M, Bromham N, et al. The effectiveness of buprenorphine for treating cancer pain: an abridged Cochrane review. BMJ Support Palliat Care 2016; 6:292.
  10. Prommer EE. Tramadol: does it have a role in cancer pain management? J Opioid Manag 2005; 1:131.
  11. Rodriguez RF, Castillo JM, Castillo MP, et al. Hydrocodone/acetaminophen and tramadol chlorhydrate combination tablets for the management of chronic cancer pain: a double-blind comparative trial. Clin J Pain 2008; 24:1.
  12. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database Syst Rev 2015; :CD011460.
  13. Quigley C. Opioids in people with cancer-related pain. BMJ Clin Evid 2008; 2008.
  14. WHO analgesic pain ladder available online. www.who.int/cancer/palliative/painladder/en/ (Accessed on September 06, 2011).
  15. Straube C, Derry S, Jackson KC, et al. Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database Syst Rev 2014; :CD006601.
  16. Maltoni M, Scarpi E, Modonesi C, et al. A validation study of the WHO analgesic ladder: a two-step vs three-step strategy. Support Care Cancer 2005; 13:888.
  17. Bandieri E, Romero M, Ripamonti CI, et al. Randomized Trial of Low-Dose Morphine Versus Weak Opioids in Moderate Cancer Pain. J Clin Oncol 2016; 34:436.
  18. Otton SV, Schadel M, Cheung SW, et al. CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clin Pharmacol Ther 1993; 54:463.
  19. de Leon J, Dinsmore L, Wedlund P. Adverse drug reactions to oxycodone and hydrocodone in CYP2D6 ultrarapid metabolizers. J Clin Psychopharmacol 2003; 23:420.
  20. Lötsch J, Rohrbacher M, Schmidt H, et al. Can extremely low or high morphine formation from codeine be predicted prior to therapy initiation? Pain 2009; 144:119.
  21. Nicholson AB. Methadone for cancer pain. Cochrane Database Syst Rev 2007; :CD003971.
  22. Mercadante S, Tirelli W, David F, et al. Morphine versus oxycodone in pancreatic cancer pain: a randomized controlled study. Clin J Pain 2010; 26:794.
  23. Pigni A, Brunelli C, Caraceni A. The role of hydromorphone in cancer pain treatment: a systematic review. Palliat Med 2011; 25:471.
  24. Riley J, Branford R, Droney J, et al. Morphine or oxycodone for cancer-related pain? A randomized, open-label, controlled trial. J Pain Symptom Manage 2015; 49:161.
  25. Corli O, Floriani I, Roberto A, et al. Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids. Ann Oncol 2016; 27:1107.
  26. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database Syst Rev 2016; 4:CD003868.
  27. Bao YJ, Hou W, Kong XY, et al. Hydromorphone for cancer pain. Cochrane Database Syst Rev 2016; 10:CD011108.
  28. Sjögren P. Clinical implications of morphine metabolites. In: Topics in Palliative Care Vol 1, Portenoy RK, Bruera EB (Eds), Oxford University Press, New York 1997. p.163.
  29. Penson RT, Joel SP, Gloyne A, et al. Morphine analgesia in cancer pain: role of the glucuronides. J Opioid Manag 2005; 1:83.
  30. Quigley C, Joel S, Patel N, et al. Plasma concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide and their relationship with analgesia and side effects in patients with cancer-related pain. Palliat Med 2003; 17:185.
  31. Penson RT, Joel SP, Bakhshi K, et al. Randomized placebo-controlled trial of the activity of the morphine glucuronides. Clin Pharmacol Ther 2000; 68:667.
  32. Sjøgren P, Thunedborg LP, Christrup L, et al. Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration? Six case histories. Acta Anaesthesiol Scand 1998; 42:1070.
  33. Schmidt-Hansen M, Bennett MI, Arnold S, et al. Oxycodone for cancer-related pain. Cochrane Database Syst Rev 2015; :CD003870.
  34. Schmidt-Hansen M, Bennett MI, Hilgart J. Oxycodone for Cancer Pain in Adult Patients. JAMA 2015; 314:1282.
  35. Quigley C, Wiffen P. A systematic review of hydromorphone in acute and chronic pain. J Pain Symptom Manage 2003; 25:169.
  36. Mayyas F, Fayers P, Kaasa S, Dale O. A systematic review of oxymorphone in the management of chronic pain. J Pain Symptom Manage 2010; 39:296.
  37. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm372287.htm (Accessed on October 29, 2013).
  38. Baek SK, Shin HW, Choi YJ, et al. Noninterventional observational study using high-dose controlled-release oxycodone (CR oxycodone) for cancer pain management in outpatient clinics. Pain Med 2013; 14:1866.
  39. Abuse-Deterrent Opioid Formulations. JAMA 2015; 314:1744.
  40. Wirz S, Wittmann M, Schenk M, et al. Gastrointestinal symptoms under opioid therapy: a prospective comparison of oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine. Eur J Pain 2009; 13:737.
  41. Ahmedzai S, Brooks D. Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. J Pain Symptom Manage 1997; 13:254.
  42. van Seventer R, Smit JM, Schipper RM, et al. Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain. Curr Med Res Opin 2003; 19:457.
  43. Wong JO, Chiu GL, Tsao CJ, Chang CL. Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain. Acta Anaesthesiol Sin 1997; 35:25.
  44. Tassinari D, Sartori S, Tamburini E, et al. Transdermal fentanyl as a front-line approach to moderate-severe pain: a meta-analysis of randomized clinical trials. J Palliat Care 2009; 25:172.
  45. Tassinari D, Sartori S, Tamburini E, et al. Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature. J Palliat Med 2008; 11:492.
  46. Hadley G, Derry S, Moore RA, Wiffen PJ. Transdermal fentanyl for cancer pain. Cochrane Database Syst Rev 2013; :CD010270.
  47. FDA Public Health Advisory. Risk of burns during MRI scans from transdermal drug patches with metallic backings. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm111313.htm (Accessed on January 03, 2012).
  48. Bryson J, Tamber A, Seccareccia D, Zimmermann C. Methadone for treatment of cancer pain. Curr Oncol Rep 2006; 8:282.
  49. Leppert W. The role of methadone in cancer pain treatment--a review. Int J Clin Pract 2009; 63:1095.
  50. Salpeter SR, Buckley JS, Bruera E. The use of very-low-dose methadone for palliative pain control and the prevention of opioid hyperalgesia. J Palliat Med 2013; 16:616.
  51. Bruera E, Palmer JL, Bosnjak S, et al. Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study. J Clin Oncol 2004; 22:185.
  52. Connolly I, Zaleon C, Montagnini M. Management of severe neuropathic cancer pain: an illustrative case and review. Am J Hosp Palliat Care 2013; 30:83.
  53. Practical Pain Management 2015; 15(2): Practical guide to the safe use of methadone. Article available online at http://www.practicalpainmanagement.com/treatments/pharmacological/opioids/practical-guide-safe-use-methadone (Accessed on October 21, 2015).
  54. Cruciani RA. Methadone: to ECG or not to ECG...That is still the question. J Pain Symptom Manage 2008; 36:545.
  55. Reddy S, Hui D, El Osta B, et al. The effect of oral methadone on the QTc interval in advanced cancer patients: a prospective pilot study. J Palliat Med 2010; 13:33.
  56. Krantz MJ, Martin J, Stimmel B, et al. QTc interval screening in methadone treatment. Ann Intern Med 2009; 150:387.
  57. Chou R, Cruciani RA, Fiellin DA, et al. Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. J Pain 2014; 15:321.
  58. Chou R, Clark E, Helfand M. Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. J Pain Symptom Manage 2003; 26:1026.
  59. Chan GL, Matzke GR. Effects of renal insufficiency on the pharmacokinetics and pharmacodynamics of opioid analgesics. Drug Intell Clin Pharm 1987; 21:773.
  60. Launay-Vacher V, Karie S, Fau JB, et al. Treatment of pain in patients with renal insufficiency: the World Health Organization three-step ladder adapted. J Pain 2005; 6:137.
  61. Kurita GP, Lundström S, Sjøgren P, et al. Renal function and symptoms/adverse effects in opioid-treated patients with cancer. Acta Anaesthesiol Scand 2015; 59:1049.
  62. Lee KA, Ganta N, Horton JR, Chai E. Evidence for Neurotoxicity Due to Morphine or Hydromorphone Use in Renal Impairment: A Systematic Review. J Palliat Med 2016; 19:1179.
  63. Kullgren J, Le V, Wheeler W. Incidence of hydromorphone-induced neuroexcitation in hospice patients. J Palliat Med 2013; 16:1205.
  64. Lee MA, Leng ME, Tiernan EJ. Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine. Palliat Med 2001; 15:26.
  65. Paramanandam G, Prommer E, Schwenke DC. Adverse effects in hospice patients with chronic kidney disease receiving hydromorphone. J Palliat Med 2011; 14:1029.
  66. Oliverio C, Malone N, Rosielle DA. Opoid use in liver failure #260. J Palliat Med 2012; 15:1389.
  67. Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999; 81:129.
  68. Caraceni A, Martini C, Zecca E, et al. Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliat Med 2004; 18:177.
  69. Rauck R, North J, Gever LN, et al. Fentanyl buccal soluble film (FBSF) for breakthrough pain in patients with cancer: a randomized, double-blind, placebo-controlled study. Ann Oncol 2010; 21:1308.
  70. Fallon M, Reale C, Davies A, et al. Efficacy and safety of fentanyl pectin nasal spray compared with immediate-release morphine sulfate tablets in the treatment of breakthrough cancer pain: a multicenter, randomized, controlled, double-blind, double-dummy multiple-crossover study. J Support Oncol 2011; 9:224.
  71. Rauck R, Reynolds L, Geach J, et al. Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin 2012; 28:859.
  72. Jandhyala R, Fullarton JR, Bennett MI. Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials. J Pain Symptom Manage 2013; 46:573.
  73. Portenoy RK, Burton AW, Gabrail N, et al. A multicenter, placebo-controlled, double-blind, multiple-crossover study of Fentanyl Pectin Nasal Spray (FPNS) in the treatment of breakthrough cancer pain. Pain 2010; 151:617.
  74. Webster LR, Slevin KA, Narayana A, et al. Fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic cancer and noncancer pain: a randomized, double-blind, crossover study followed by a 12-week open-label phase to evaluate patient outcomes. Pain Med 2013; 14:1332.
  75. Kosugi T, Hamada S, Takigawa C, et al. A randomized, double-blind, placebo-controlled study of fentanyl buccal tablets for breakthrough pain: efficacy and safety in Japanese cancer patients. J Pain Symptom Manage 2014; 47:990.
  76. Mercadante S, Adile C, Cuomo A, et al. Fentanyl Buccal Tablet vs. Oral Morphine in Doses Proportional to the Basal Opioid Regimen for the Management of Breakthrough Cancer Pain: A Randomized, Crossover, Comparison Study. J Pain Symptom Manage 2015; 50:579.
  77. Vasisht N, Gever LN, Tagarro I, Finn AL. Formulation selection and pharmacokinetic comparison of fentanyl buccal soluble film with oral transmucosal fentanyl citrate: a randomized, open-label, single-dose, crossover study. Clin Drug Investig 2009; 29:647.
  78. Bohme K, Likar R. Efficacy and tolerability of a new opioid fomulation, buprenorphine transdermal therapeutic system (TDS) in the treatment of patients with chronic pain. A randomised, double-blind, placebo-controlled study. Pain Clin 2003; 15:193.
  79. Sorge J, Sittl R. Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Clin Ther 2004; 26:1808.
  80. Naing C, Aung K, Racloz V, Yeoh PN. Safety and efficacy of transdermal buprenorphine for the relief of cancer pain. J Cancer Res Clin Oncol 2013; 139:1963.
  81. Bruera E, Fainsinger R, Spachynski K, et al. Clinical efficacy and safety of a novel controlled-release morphine suppository and subcutaneous morphine in cancer pain: a randomized evaluation. J Clin Oncol 1995; 13:1520.
  82. Walsh D, Tropiano PS. Long-term rectal administration of high-dose sustained-release morphine tablets. Support Care Cancer 2002; 10:653.
  83. Wilkinson TJ, Robinson BA, Begg EJ, et al. Pharmacokinetics and efficacy of rectal versus oral sustained-release morphine in cancer patients. Cancer Chemother Pharmacol 1992; 31:251.
  84. Moolenaar F, Meijler WJ, Frijlink HW, et al. Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain. Eur J Clin Pharmacol 2000; 56:219.
  85. Wilcock A, Jacob JK, Charlesworth S, et al. Drugs given by a syringe driver: a prospective multicentre survey of palliative care services in the UK. Palliat Med 2006; 20:661.
  86. McNeill JA, Sherwood GD, Starck PL. The hidden error of mismanaged pain: a systems approach. J Pain Symptom Manage 2004; 28:47.
  87. Sloan PA. Neuraxial pain relief for intractable cancer pain. Curr Pain Headache Rep 2007; 11:283.
  88. Smith TJ, Staats PS, Deer T, et al. 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 2002; 20:4040.
  89. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
  90. Fine P, Portenoy RK. Opioid analgesia. New York: McGraw Hill, 2004. http://www.stoppain.org/pcd/content/forpros/opioidbook.asp (Accessed on April 21, 2011).
  91. Jost L, Roila F, ESMO Guidelines Working Group. Management of cancer pain: ESMO clinical recommendations. Ann Oncol 2008; 19 Suppl 2:ii119.
  92. Krakowski I, Theobald S, Balp L, et al. Summary version of the Standards, Options and Recommendations for the use of analgesia for the treatment of nociceptive pain in adults with cancer (update 2002). Br J Cancer 2003; 89 Suppl 1:S67.
  93. Cormie PJ, Nairn M, Welsh J, Guideline Development Group. Control of pain in adults with cancer: summary of SIGN guidelines. BMJ 2008; 337:a2154.
  94. Zeppetella G. Impact and management of breakthrough pain in cancer. Curr Opin Support Palliat Care 2009; 3:1.
  95. William L, Macleod R. Management of breakthrough pain in patients with cancer. Drugs 2008; 68:913.
  96. Mercadante S, Portenoy RK. Opioid poorly-responsive cancer pain. Part 1: clinical considerations. J Pain Symptom Manage 2001; 21:144.
  97. Sacks T, Weissman DE, Arnold RM. Opioid poorly responsive cancer pain #215. J Palliat Med 2013; 16:696.
  98. Mercadante S, Portenoy RK. Opioid poorly-responsive cancer pain. Part 3. Clinical strategies to improve opioid responsiveness. J Pain Symptom Manage 2001; 21:338.
  99. Reddy A, Yennurajalingam S, Pulivarthi K, et al. Frequency, outcome, and predictors of success within 6 weeks of an opioid rotation among outpatients with cancer receiving strong opioids. Oncologist 2013; 18:212.
  100. Knotkova H, Fine PG, Portenoy RK. Opioid rotation: the science and the limitations of the equianalgesic dose table. J Pain Symptom Manage 2009; 38:426.
  101. Fine PG, Portenoy RK, Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. Establishing "best practices" for opioid rotation: conclusions of an expert panel. J Pain Symptom Manage 2009; 38:418.
  102. Indelicato RA, Portenoy RK. Opioid rotation in the management of refractory cancer pain. J Clin Oncol 2002; 20:348.
  103. Chatham MS, Dodds Ashley ES, Svengsouk JS, Juba KM. Dose ratios between high dose oral morphine or equivalents and oral methadone. J Palliat Med 2013; 16:947.
  104. Lawlor PG, Turner KS, Hanson J, Bruera ED. Dose ratio between morphine and methadone in patients with cancer pain: a retrospective study. Cancer 1998; 82:1167.
  105. Ripamonti C, De Conno F, Groff L, et al. Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: comparison of two clinical experiences. Ann Oncol 1998; 9:79.
  106. Benítez-Rosario MA, Salinas-Martín A, Aguirre-Jaime A, et al. Morphine-methadone opioid rotation in cancer patients: analysis of dose ratio predicting factors. J Pain Symptom Manage 2009; 37:1061.
  107. Mercadante S, Casuccio A, Calderone L. Rapid switching from morphine to methadone in cancer patients with poor response to morphine. J Clin Oncol 1999; 17:3307.
  108. Mercadante S, Casuccio A, Fulfaro F, et al. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. J Clin Oncol 2001; 19:2898.
  109. Parsons HA, de la Cruz M, El Osta B, et al. Methadone initiation and rotation in the outpatient setting for patients with cancer pain. Cancer 2010; 116:520.
  110. McLean S, Twomey F. Methods of Rotation From Another Strong Opioid to Methadone for the Management of Cancer Pain: A Systematic Review of the Available Evidence. J Pain Symptom Manage 2015; 50:248.
  111. Moksnes K, Dale O, Rosland JH, et al. How to switch from morphine or oxycodone to methadone in cancer patients? a randomised clinical phase II trial. Eur J Cancer 2011; 47:2463.