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Breakthrough pain and rapid-onset opioids in patients with cancer pain: a narrative review

  • Jinseok Yeo (Department of Anesthesiology and Pain Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University)
  • Received : 2023.04.03
  • Accepted : 2023.05.19
  • Published : 2024.01.31

Abstract

Breakthrough pain is transitory pain that occurs despite the use of opioids for background pain control. Breakthrough pain occurs in 40% to 80% of patients with cancer pain. Despite effective analgesic therapy, patients and their caregivers often feel that their pain is not sufficiently controlled. Therefore, an improved understanding of breakthrough pain and its management is essential for all physicians caring for patients with cancer. This article reviews the definition, clinical manifestations, accurate diagnostic strategies, and optimal treatment options for breakthrough pain in patients with cancer. This review focuses on the efficacy and safety of rapid-onset opioids, which are the primary rescue drugs for breakthrough pain.

Keywords

References

  1. van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan-Heijnen VC, Janssen DJ. Update on prevalence of pain in patients with cancer: systematic review and meta-analysis. J Pain Symptom Manage 2016;51:1070-90. https://doi.org/10.1016/j.jpainsymman.2015.12.340
  2. van den Beuken-van Everdingen MH, van Kuijk SM, Janssen DJ, Joosten EA. Treatment of pain in cancer: towards personalised medicine. Cancers (Basel) 2018;10:502.
  3. Muller-Schwefe G, Ahlbeck K, Aldington D, Alon E, Coaccioli S, Coluzzi F, et al. Pain in the cancer patient: different pain characteristics CHANGE pharmacological treatment requirements. Curr Med Res Opin 2014;30:1895-908. https://doi.org/10.1185/03007995.2014.925439
  4. Caraceni A, Martini C, Zecca E, Portenoy RK, Ashby MA, Hawson G, et al. Breakthrough pain characteristics and syndromes in patients with cancer pain: an international survey. Palliat Med 2004;18:177-83. https://doi.org/10.1191/0269216304pm890oa
  5. Greco MT, Roberto A, Corli O, Deandrea S, Bandieri E, Cavuto S, et al. Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. J Clin Oncol 2014;32:4149-54. https://doi.org/10.1200/JCO.2014.56.0383
  6. Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G; Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain 2009;13:331-8. https://doi.org/10.1016/j.ejpain.2008.06.014
  7. Fortner BV, Demarco G, Irving G, Ashley J, Keppler G, Chavez J, et al. Description and predictors of direct and indirect costs of pain reported by cancer patients. J Pain Symptom Manage 2003;25:9-18. https://doi.org/10.1016/S0885-3924(02)00597-3
  8. Portenoy RK, Hagen NA. Breakthrough pain: definition, prevalence and characteristics. Pain 1990;41:273-81. https://doi.org/10.1016/0304-3959(90)90004-W
  9. Coluzzi PH. Cancer pain management: newer perspectives on opioids and episodic pain. Am J Hosp Palliat Care 1998;15:13-22. https://doi.org/10.1177/104990919801500105
  10. Davies AN, Elsner F, Filbet MJ, Porta-Sales J, Ripamonti C, Santini D, et al. Breakthrough cancer pain (BTcP) management: a review of international and national guidelines. BMJ Support Palliat Care 2018;8:241-9. https://doi.org/10.1136/bmjspcare-2017-001467
  11. National Comprehensive Cancer Network (NCCN). Adult cancer pain: version 1 [Internet]. Fort Washington, PA: NCCN; 2023 [cited 2023 Apr 23]. https://www.nccn.org/professionals/physician_gls/pdf/pain.pdf.
  12. Mercadante S, Radbruch L, Caraceni A, Cherny N, Kaasa S, Nauck F, et al. Episodic (breakthrough) pain: consensus conference of an expert working group of the European Association for Palliative Care. Cancer 2002;94:832-9. https://doi.org/10.1002/cncr.10249
  13. Lohre ET, Klepstad P, Bennett MI, Brunelli C, Caraceni A, Fainsinger RL, et al. From "breakthrough" to "episodic" cancer pain?: a European Association for Palliative Care Research Network Expert Delphi Survey toward a common terminology and classification of transient cancer pain exacerbations. J Pain Symptom Manage 2016;51:1013-9. https://doi.org/10.1016/j.jpainsymman.2015.12.329
  14. Davies A, Buchanan A, Zeppetella G, Porta-Sales J, Likar R, Weismayr W, et al. Breakthrough cancer pain: an observational study of 1000 European oncology patients. J Pain Symptom Manage 2013;46:619-28. https://doi.org/10.1016/j.jpainsymman.2012.12.009
  15. Mercadante S, Lazzari M, Reale C, Cuomo A, Fusco F, Marchetti P, et al. Italian Oncological Pain Survey (IOPS): a multicentre Italian study of breakthrough pain performed in different settings. Clin J Pain 2015;31:214-21. https://doi.org/10.1097/AJP.0000000000000161
  16. Saini A, Tucci M, Tampellini M, Maina D, Bouraouia K, Giuliano PL, et al. Circadian variation of breakthrough pain in cancer patients. Eur J Pain 2013;17:264-70. https://doi.org/10.1002/j.1532-2149.2012.00184.x
  17. Boceta J, De la Torre A, Samper D, Farto M, Sanchez-de la Rosa R. Consensus and controversies in the definition, assessment, treatment and monitoring of BTcP: results of a Delphi study. Clin Transl Oncol 2016;18:1088-97. https://doi.org/10.1007/s12094-016-1490-4
  18. Smith H. A comprehensive review of rapid-onset opioids for breakthrough pain. CNS Drugs 2012;26:509-35. https://doi.org/10.2165/11630580-000000000-00000
  19. Davies A, Zeppetella G, Andersen S, Damkier A, Vejlgaard T, Nauck F, et al. Multi-centre European study of breakthrough cancer pain: pain characteristics and patient perceptions of current and potential management strategies. Eur J Pain 2011;15:756-63. https://doi.org/10.1016/j.ejpain.2010.12.004
  20. Deandrea S, Corli O, Consonni D, Villani W, Greco MT, Apolone G. Prevalence of breakthrough cancer pain: a systematic review and a pooled analysis of published literature. J Pain Symptom Manage 2014;47:57-76. https://doi.org/10.1016/j.jpainsymman.2013.02.015
  21. Svendsen KB, Andersen S, Arnason S, Arner S, Breivik H, Heiskanen T, et al. Breakthrough pain in malignant and nonmalignant diseases: a review of prevalence, characteristics and mechanisms. Eur J Pain 2005;9:195-206. https://doi.org/10.1016/j.ejpain.2004.06.001
  22. Soden K, Ali S, Alloway L, Barclay D, Perkins P, Barker S. How do nurses assess and manage breakthrough pain in specialist palliative care inpatient units?: a multicentre study. Palliat Med 2010;24:294-8. https://doi.org/10.1177/0269216309355918
  23. Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, et al. Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage 2011;41:1073-93. https://doi.org/10.1016/j.jpainsymman.2010.08.016
  24. Brunelli C, Zecca E, Martini C, Campa T, Fagnoni E, Bagnasco M, et al. Comparison of numerical and verbal rating scales to measure pain exacerbations in patients with chronic cancer pain. Health Qual Life Outcomes 2010;8:42.
  25. Mercadante S, Adile C, Torta R, Varetto A, Fulfaro F, Giarratano A, et al. Meaningful cut-off pain intensity for breakthrough pain changes in advanced cancer patients. Curr Med Res Opin 2013;29:93-7. https://doi.org/10.1185/03007995.2012.755120
  26. Daeninck P, Gagnon B, Gallagher R, Henderson JD, Shir Y, Zimmermann C, et al. Canadian recommendations for the management of breakthrough cancer pain. Curr Oncol 2016; 23:96-108. https://doi.org/10.3747/co.23.2865
  27. Webber K, Davies AN, Cowie MR. Accuracy of a diagnostic algorithm to diagnose breakthrough cancer pain as compared with clinical assessment. J Pain Symptom Manage 2015;50:495-500. https://doi.org/10.1016/j.jpainsymman.2015.05.006
  28. Hagen NA, Stiles C, Nekolaichuk C, Biondo P, Carlson LE, Fisher K, et al. The Alberta Breakthrough Pain Assessment Tool for cancer patients: a validation study using a Delphi process and patient think-aloud interviews. J Pain Symptom Manage 2008;35:136-52. https://doi.org/10.1016/j.jpainsymman.2007.03.016
  29. Webber K, Davies AN, Zeppetella G, Cowie MR. Development and validation of the breakthrough pain assessment tool (BAT) in cancer patients. J Pain Symptom Manage 2014;48:619-31. https://doi.org/10.1016/j.jpainsymman.2013.10.026
  30. Ahmad I, Ahmed MM, Ahsraf MF, Naeem A, Tasleem A, Ahmed M, et al. Pain management in metastatic bone disease: a literature review. Cureus 2018;10:e3286.
  31. Mazzotta M, Filetti M, Piras M, Mercadante S, Marchetti P, Giusti R. Patients' satisfaction with breakthrough cancer pain therapy: a secondary analysis of IOPS-MS Study. Cancer Manag Res 2022;14:1237-45. https://doi.org/10.3390/cancers14051237
  32. Mercadante S. Pharmacotherapy for breakthrough cancer pain. Drugs 2012;72:181-90. https://doi.org/10.2165/11597260-000000000-00000
  33. Zeppetella G. Dynamics of breakthrough pain vs. pharmacokinetics of oral morphine: implications for management. Eur J Cancer Care (Engl) 2009;18:331-7. https://doi.org/10.1111/j.1365-2354.2008.01009.x
  34. Mercadante S, Villari P, Ferrera P, Porzio G, Aielli F, Verna L, et al. Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine. J Pain Symptom Manage 2006;32:175-9. https://doi.org/10.1016/j.jpainsymman.2006.01.013
  35. Stanley TH. The fentanyl story. J Pain 2014;15:1215-26. https://doi.org/10.1016/j.jpain.2014.08.010
  36. Lotsch J. Pharmacokinetic-pharmacodynamic modeling of opioids. J Pain Symptom Manage 2005;29(5 Suppl):S90-103. https://doi.org/10.1016/j.jpainsymman.2005.01.012
  37. Streisand JB, Busch MA, Egan TD, Smith BG, Gay M, Pace NL. Dose proportionality and pharmacokinetics of oral transmucosal fentanyl citrate. Anesthesiology 1998;88:305-9. https://doi.org/10.1097/00000542-199802000-00006
  38. Darwish M, Messina J. Clinical pharmacology of fentanyl buccal tablet for the treatment of breakthrough pain. Expert Rev Clin Pharmacol 2008;1:39-47. https://doi.org/10.1586/17512433.1.1.39
  39. Portenoy RK, Taylor D, Messina J, Tremmel L. A randomized, placebo-controlled study of fentanyl buccal tablet for breakthrough pain in opioid-treated patients with cancer. Clin J Pain 2006;22:805-11. https://doi.org/10.1097/01.ajp.0000210932.27945.4a
  40. Chwieduk CM, McKeage K. Fentanyl sublingual: in breakthrough pain in opioid-tolerant adults with cancer. Drugs 2010;70:2281-8. https://doi.org/10.2165/11200910-000000000-00000
  41. Davies A, Mundin G, Vriens J, Webber K, Buchanan A, Waghorn M. The influence of low salivary flow rates on the absorption of a sublingual fentanyl citrate formulation for breakthrough cancer pain. J Pain Symptom Manage 2016;51:538-45. https://doi.org/10.1016/j.jpainsymman.2015.11.018
  42. Foster D, Upton R, Christrup L, Popper L. Pharmacokinetics and pharmacodynamics of intranasal versus intravenous fentanyl in patients with pain after oral surgery. Ann Pharmacother 2008;42:1380-7. https://doi.org/10.1345/aph.1L168
  43. Panagiotou I, Mystakidou K. Intranasal fentanyl: from pharmacokinetics and bioavailability to current treatment applications. Expert Rev Anticancer Ther 2010;10:1009-21. https://doi.org/10.1586/era.10.77
  44. Lotsch J, Walter C, Parnham MJ, Oertel BG, Geisslinger G. Pharmacokinetics of non-intravenous formulations of fentanyl. Clin Pharmacokinet 2013;52:23-36. https://doi.org/10.1007/s40262-012-0016-7
  45. Zeppetella G, Davies A, Eijgelshoven I, Jansen JP. A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes. J Pain Symptom Manage 2014;47:772-85. https://doi.org/10.1016/j.jpainsymman.2013.05.020
  46. Mercadante S, Adile C, Masedu F, Marchetti P, Costanzi A, Aielli F. Factors influencing the use of opioids for breakthrough cancer pain: a secondary analysis of the IOPS-MS study. Eur J Pain 2019;23:719-26. https://doi.org/10.1002/ejp.1339
  47. Cuomo A, Cascella M, Forte CA, Bimonte S, Esposito G, De Santis S, et al. Careful breakthrough cancer pain treatment through rapid-onset transmucosal fentanyl improves the quality of life in cancer patients: results from the BEST Multicenter Study. J Clin Med 2020;9:1003.
  48. Mercadante S, Gatti A, Porzio G, Lo Presti C, Aielli F, Adile C, et al. Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus proportional doses. Curr Med Res Opin 2012;28:963-8. https://doi.org/10.1185/03007995.2012.683112
  49. Yen TY, Chiou JF, Chiang WY, Su WH, Huang MY, Hu MH, et al. Proportional dose of rapid-onset opioid in breakthrough cancer pain management: an open-label, multicenter study. Medicine (Baltimore) 2018;97:e11593.
  50. Mercadante S, Maltoni M, Russo D, Adile C, Ferrera P, Rossi R, et al. The prevalence and characteristics of breakthrough cancer pain in patients receiving low doses of opioids for background pain. Cancers (Basel) 2021;13:1058.
  51. Passik SD, Kirsh KL. Weighing in on the off-label use of Actiq for noncancer-related pain: a recipe for success or a recipe for disaster? Pain Med 2007;8:130-3. https://doi.org/10.1111/j.1526-4637.2006.00295.x
  52. Mercadante S, Adile C, Cuomo A, Aielli F, Marinangeli F, Casuccio A. The use of low doses of a sublingual fentanyl formulation for breakthrough pain in patients receiving low doses of opioids. Support Care Cancer 2017;25:645-9. https://doi.org/10.1007/s00520-016-3457-y
  53. Preux C, Bertin M, Tarot A, Authier N, Pinol N, Brugnon D, et al. Prevalence of opioid use disorder among patients with cancer-related pain: a systematic review. J Clin Med 2022;11:1594.