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Opioids for the management of breakthrough pain in cancer patients

  1. Giovambattista Zeppetella1,*,
  2. Andrew N Davies2

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 21 OCT 2013

Assessed as up-to-date: 18 OCT 2013

DOI: 10.1002/14651858.CD004311.pub3


How to Cite

Zeppetella G, Davies AN. Opioids for the management of breakthrough pain in cancer patients. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD004311. DOI: 10.1002/14651858.CD004311.pub3.

Author Information

  1. 1

    St Clare Hospice, Hastingwood, Essex, UK

  2. 2

    Royal Surrey County Hospital, Department of Palliative Medicine, Guildford, UK

*Giovambattista Zeppetella, St Clare Hospice, Hastingwood Road, Hastingwood, Essex, CM17 9JX, UK. John.Zeppetella@stclarehospice.org.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions), comment added to review
  2. Published Online: 21 OCT 2013

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This is not the most recent version of the article. View current version (14 AUG 2015)

References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Christie 1998 {published data only}
  • Christie JM, Simmonds M, Patt R, Coluzzi P, Busch MA, Nordbrock E, et al. Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. Journal of Clinical Oncology 1998;16(10):3238-45.
Coluzzi 2001 {published data only}
  • Coluzzi PH, Schwartzberg L, Conroy JD, Charapata S, Gay M, Busch MA, et al. Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR). Douleurs 2002;3(1):26-35.
  • Coluzzi PH, Schwartzberg L, Conroy JD, Charapata S, Gay M, Busch MA, et al. Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR). Pain 2001;91(1-2):123-30.
Fallon 2011 {published data only}
  • Fallon M, Reale C, Davies A, Lux AE, Kumar K, Stachowiak 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. Journal of Supportive Oncology 2011;9(6):224-31.
Farrar 1998 {published data only}
  • Farrar JT, Cleary J, Rauck R, Busch M, Nordbrock E. Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients. Journal of the National Cancer Institute 1998;90(8):611-6.
Kress 2009 {published data only}
  • Kress HG, Orońska A, Kaczmarek Z, Kaasa S, Colberg T, Nolte T. Efficacy and tolerability of intranasal fentanyl spray 50 to 200 microg for breakthrough pain in patients with cancer: a phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10-month, open-label extension treatment period. Clinical Therapeutics 2009;31(6):1177-91.
Lennernäs 2010 {published data only}
  • Lennernäs B, Frank-Lissbrant I, Lennernäs H, Kälkner KM, Derrick R, Howell J. Sublingual administration of fentanyl to cancer patients is an effective treatment for breakthrough pain: results from a randomized phase II study. Palliative Medicine 2010;24(3):286-93.
Mercadante 2007 {published data only}
  • Mercadante S, Villari P, Ferrera P, Casuccio A, Mangione S, Intravaia G. Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain. British Journal of Cancer 2007;96(12):1828-33.
Mercadante 2009 {published data only}
  • Mercadante S, Radbruch L, Davies A, Poulain P, Sitte T, Perkins P, et al. A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial. Current Medical Research and Opinion 2009;25(11):2805-15.
Portenoy 1999a {published data only}
  • Portenoy RK, Payne R, Coluzzi P, Raschko JW, Lyss A, Busch MA, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study. Pain 1999;79(2-3):303-12.
Portenoy 2006 {published data only}
  • 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. Clinical Journal of Pain 2006;22(9):805-11.
Portenoy 2010 {published data only}
  • Portenoy RK, Burton AW, Gabrail N, Taylor D. Fentanyl Pectin Nasal Spray 043 Study Group. 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(3):617-24.
Rauch 2009 {published data only}
  • Rauck RL, Tark M, Reyes E, Hayes TG, Bartkowiak AJ, Hassman D, et al. Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Current Medical Research and Opinion 2009;25(12):2877-85.
Rauch 2010 {published data only}
  • Rauck R, North J, Gever LN, Tagarro I, Finn AL. Fentanyl buccal soluble film (FBSF) for breakthrough pain in patients with cancer: a randomized, double-blind, placebo-controlled study. Annals of Oncology 2010;21(6):1308-14.
Rauch 2012 {published data only}
  • Rauch R, Reynolds L, Geach J, Bull J, Stearns L, Scherlis M, et al. Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study. Current Medical Research and Opinion 2012;28(5):859-70.
Slatkin 2007 {published data only}
  • Slatkin NE, Xie F, Messina J, Segal TJ. Fentanyl buccal tablet for relief of breakthrough pain in opioid-tolerant patients with cancer-related chronic pain. Journal of Supportive Oncology 2007;5(7):327-34.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Ashburn 2011 {published data only}
  • Ashburn MA, Slevin KA, Messina J, Xie F. The efficacy and safety of fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic pain. Anaesthesia and Analgesia 2011;112(3):693-702.
Cleary 1997 {published data only}
  • Cleary JF. Double blind, randomized study of the treatment of breakthrough pain in cancer patients: oral transmucosal fentanyl citrate versus placebo. Proceedings of the American Society of Clinical Oncology 1997;16:52a.
Coluzzi 1997 {published data only}
  • Coluzzi P. A titration study of oral transmucosal fentanyl citrate for breakthrough pain in cancer patients. Proceedings of the American Society of Clinical Oncology 1997;16:52a.
Coluzzi 2002 {published data only}
  • Coluzzi PH, Schwartzberg L, Conroy Jr JD, Charapata S, Gay M, Busch MA, et al. A randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR) [Les acces douloureux paroxystiques chez les patients cancereux: essai randomise comparant le citrate de fentanyl par voie orale transmuqueuse (OTFC) et le sulfate de morphine a liberation immediate (MLI)]. Douleurs 2002;3(1):26-35.
Davies 2011 {published data only}
  • Davies A, Sitte T, Elsner F, Reale C, Espinosa J, Brooks D, et al. Consistency of efficacy, patient acceptability, and nasal tolerability of fentanyl pectin nasal spray compared with immediate-release morphine sulfate in breakthrough cancer pain. Journal of Pain and Symptom Management 2011;41(2):358-66.
Hagen 2010 {published data only}
  • Hagen NA, Moulin DE, Brasher PM, Biondo PD, Eliasziw M, Watanabe SM, et al. A formal feasibility study of sublingual methadone for breakthrough cancer pain. Palliative Medicine 2010;24(7):696-706.
Johnson 2010 {published data only}
  • Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management 2010;39(2):167-79.
Pasqualucci 1987 {published data only}
  • Pasqualucci V, Tantucci C, Paoletti F, Dottorini ML, Bifarini G, Belfiore R, et al. Buprenorphine vs. morphine via the epidural route: a controlled clinical study of respiratory effects and analgesic activity. Pain 1987;29(3):273-86.
Rauch 2011 {published data only}
  • Rauck R, Stearns L, Scherlis M, Parikh N, Dillaha L. Fentanyl sublingual (SL) spray: reduction of breakthrough cancer pain 5-minutes post dose. Journal of Pain 2011;4 (Suppl):P50.
Rauch 2012b {published data only}
  • Rauck R, Stearns L, Scherlis M, Parikh N, Dillaha L. Reduction of breakthrough cancer pain at 5 minutes post dose. Pain Practice 2012;12:192-3.
Reynolds 2011 {published data only}
  • Reynolds L, Geach J, Parikh N, Dillaha L, Bull J. Safety and efficacy of fentanyl sublingual (SL) spray in the treatment of breakthrough cancer pain. Journal of Pain 2011;12(4 Suppl):P50.
Reynolds 2012 {published data only}
  • Reynolds L, Geach J, Parikh N, Dillaha L, Bull J. Safety and efficacy of fentanyl sublingual (SL) spray in the treatment of breakthrough cancer pain. Pain Practice 2012;12:193.
Shaiova 2004 {published data only}
  • Shaiova L, Lapin J, Manco LS, Shasha D, Hu K, Harrison L, et al. Tolerability and effects of two formulations of oral transmucosal fentanyl citrate (OTFC; ACTIQ) in patients with radiation-induced oral mucositis. Supportive Care in Cancer 2004;12:268-73.
Simmonds 1997 {published data only}
  • Simmonds MA. Oral transmucosal fentanyl citrate produces pain relief faster than medication typically used for breakthrough pain in cancer patients. Proceedings of the American Society of Clinical Oncology 1997;16:52a.
Stanley 2011 {published data only}
  • Stanley K. Gever L. Wheeler W. Evaluation of fentanyl buccal soluble film (FBSF) in opioid tolerant cancer patients with neuropathic breakthrough cancer pain (BTP). Journal of Pain 2011;12(4 Suppl):P50.
Taylor 2010 {published data only}
  • Taylor D, Galan V, Weinstein SM, Reyes E, Pupo-Araya AR, Rauck R. Fentanyl Pectin Nasal Spray 043 Study Group. Fentanyl pectin nasal spray in breakthrough cancer pain. Journal of Supportive Oncology 2010;8(4):184-90.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Bennett 2005
  • Bennett D, Burton AW, Fishman S, Fortner B, McCarberg B, Miaskowski C, et al. Consensus panel recommendations for the assessment and management of breakthrough pain. Part 2: management. Pharmacy and Therapeutics 2005;30:354-61.
Bredenberg 2003
  • Bredenberg S, Duberg M, Lennernäs B, Lennernäs H, Pettersson A, Westerberg M, et al. In vitro and in vivo evaluation of a new sublingual tablet system for rapid oromucosal absorption using fentanyl citrate as the active substance. European Journal of Pharmaceutical Sciences 2003;20(3):327-34.
Bruera 1995
  • Bruera E, Scholler T, Wenk R, MacEachern T, Marcellino S, Hanson J, et al. A prospective multi-center assessment of the Edmonton staging system for cancer pain. Journal of Pain Symptom Management 1995;10:348-55.
Caraceni 1999
Caraceni 2012
  • Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncology 2012;13(2):58-68.
Colleau 1999
  • Colleau SM. The significance of breakthrough pain in cancer. Cancer Pain Release 1999;12(4):1-3.
Darwish 2007
Davies 2009
Diaz del Consuelo 2007
Elsner 2011
  • Elsner F, Zeppetella G, Porta-Sales J, Tagarro I. Newer generation fentanyl transmucosal products for breakthrough pain in opioid-tolerant cancer patients. Clinical Drug Investigation 2011;31(9):605-18.
Farrar 2000
Farrar 2003
Fortner 2002
  • Fortner BV, Okon TA, Portenoy RK. A survey of pain-related hospitalisations, emergency department visits, and physicians office visits reported by cancer patients with and without history of breakthrough pain. Journal of Pain 2002;3:38-44.
Fortner 2003
  • 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. Journal of Pain and Symptom Management 2003;25(1):9-18.
Hanks 2001a
  • Hanks GW, de Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, et al. Morphine and alternative opioids in cancer pain: the EAPC recommendations. British Journal of Cancer 2001;84:587-93.
Hanks 2001b
  • Hanks G. Oral transmucosal fentanyl citrate for the management of breakthrough pain. European Journal of Palliative Care 2001;8(1):6-9.
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Hwang 2003
Jadad 1996
  • Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports on randomised clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17:1-12.
McQuay 2003
Mercadante 2004
  • Mercadante S, Villari P, Ferrera P, Bianchi M, Casuccio A. Safety and effectiveness of intravenous morphine for episodic (breakthrough) pain using a fixed ratio with the oral daily morphine dose. Journal of Pain and Symptom Management 2004;27(4):353-9.
NICE 2012
  • National Institute for Health and Clinical Excellence. Opioids in palliative care: safe and effective prescribing of strong opioids for pain in palliative care of adults. NICE clinical guideline 140, 2012. guidance.nice.org.uk/CG140 (accessed 10 September 2013).
Portenoy 1989
  • Portenoy RK, Hagen NA. Breakthrough pain: definition and management. Oncology (Willison Park NY) 1989;3(8 Suppl):25-9.
Portenoy 1999b
RevMan 2012
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Savarese 1988
SIGN 2008
  • Scottish Intercollegiate Guidelines Network. Control of pain in adults with cancer pain. A national clinical guideline, 2008. www.sign.ac.uk/guidelines/fulltext/106/index.html (accessed 10 September 2013).
Watts 2009
Zeppetella 2003
Zeppetella 2008
  • Zeppetella G. Opioids for cancer breakthrough pain: a pilot study reporting patient assessment of time to meaningful pain relief. Journal of Pain and Symptom Management 2008;35:563-7.
Zeppetella 2011

References to other published versions of this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
  4. References to other published versions of this review
Zeppetella 2006