Cancer Pain Management: What’s New?

Cancer Pain (DA Marcus, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cancer Pain


Decades after the publication of the World Health Organization’s analgesic ladder, cancer pain is still a major cause of suffering for patients with cancer and affects millions of people worldwide. Owing to the increasing incidence of cancer, cancer-related pain is a major public health problem worldwide. Unfortunately, current research revealed that available options for the successful treatment of cancer pain is still massively underutilized by physicians, and many patients suffer from insufficiently controlled pain despite available treatment options. This review aims to present a concise update about new data or treatment recommendations from the field of cancer pain management. Therefore, information from guidelines, systematic reviews, and original articles that were published in the year 2012 are presented. Specifically, the publication covers information on tapentadol, fixed oxycodone/naloxone combinations, rapid onset fentanyl, nabiximols, ketamine, denusomab, and specialized psychosocial interventions including early palliative care.


Cancer pain Treatment Tapentadol Rapid onset fentanyl Psychosocial interventions Palliative care Fixed oxycodone/naloxone 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Marcus DA. Epidemiology of cancer pain. Curr Pain Headache Rep. 2011;15:231–4. doi:10.1007/s11916-011-0208-0.PubMedCrossRefGoogle Scholar
  2. 2.
    National Cancer Institute. National Cancer Institute. www. 2012. Accessed Dec, 2012.Google Scholar
  3. 3.
    World Health Organization (WHO). World Health Organization (WHO). www. 2012. Accessed Dec, 2012.Google Scholar
  4. 4.
    Shaheen PE, Legrand SB, Walsh D, Estfan B, Davis MP, Lagman RL, et al. Errors in opioid prescribing: a prospective survey in cancer pain. J Pain Symptom Man. 2010;39:702–11. doi:10.1016/j.jpainsymman.2009.09.009.CrossRefGoogle Scholar
  5. 5.
    Goudas LC, Bloch R, Gialeli-Goudas M, Lau J, Carr DB. The epidemiology of cancer pain. Cancer Invest. 2005;23:182–90.PubMedCrossRefGoogle Scholar
  6. 6.
    Breuer B, Fleishman SB, Cruciani RA, Portenoy RK. Medical oncologists’ attitudes and practice in cancer pain management: a national survey. J Clin Oncol. 2011;29:4769–75. doi:10.1200/JCO.2011.35.0561.PubMedCrossRefGoogle Scholar
  7. 7.
    Hoy SM. Tapentadol extended release: in adults with chronic pain. Drugs. 2012;72:375–93. doi:10.2165/11208600-000000000-00000.PubMedCrossRefGoogle Scholar
  8. 8.
    Kress HG. Tapentadol and its two mechanisms of action: is there a new pharmacological class of centrally-acting analgesics on the horizon? Eur J Pain. 2010;14:781–3. doi:10.1016/j.ejpain.2010.06.017.PubMedCrossRefGoogle Scholar
  9. 9.
    Afilalo M, Etropolski MS, Kuperwasser B, Kelly K, Okamoto A, Van Hove I, et al. Efficacy and safety of tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study. Clin Drug Investig. 2010;30:489–505. doi:10.2165/11533440-000000000-00000.PubMedCrossRefGoogle Scholar
  10. 10.
    Buynak R, Shapiro DY, Okamoto A, Van Hove I, Rauschkolb C, Steup A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled phase III study. Expert Opin Pharmacother. 2010;11:1787–804. doi:10.1517/14656566.2010.497720.PubMedCrossRefGoogle Scholar
  11. 11.
    Schwartz S, Etropolski M, Shapiro DY, Okamoto A, Lange R, Haeussler J, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27:151–62. doi:10.1185/03007995.2010.537589.PubMedCrossRefGoogle Scholar
  12. 12.
    • Merker M, Dinges G, Koch T, Kranke P, Morin AM. Undesired side effects of tapentadol in comparison to oxycodone. A meta-analysis of randomized controlled comparative studies. Schmerz. 2012;26:16–26. doi:10.1007/s00482-011-1132-2. First reliable meta-analysis of side effect profile of tapentadol. Relies on studies with non-cancer patients. Results from trials evaluating tapentadol for cancer pain have finished recruiting but results have not yet been published.PubMedCrossRefGoogle Scholar
  13. 13.
    Mercadante S, Porzio G, Ferrera P, Aielli F, Adile C, Ficorella C, et al. Tapentadol in cancer pain management: a prospective open-label study. Curr Med Res Opin. 2012. doi:10.1185/03007995.2012.739151.
  14. 14.
    Mercadante S, Ferrera P, Adile C. Switching from methadone to tapentadol for cancer pain. J Pain Symptom Man. 2012;44:e3–5. doi:10.1016/j.jpainsymman.2012.03.005.CrossRefGoogle Scholar
  15. 15.
    Holzer P, Ahmedzai SH, Niederle N, Leyendecker P, Hopp M, Bosse B, et al. Opioid-induced bowel dysfunction in cancer-related pain: causes, consequences, and a novel approach for its management. J Opioid Manag. 2009;5:145–51.PubMedGoogle Scholar
  16. 16.
    • Ahmedzai SH, Nauck F, Bar-Sela G, Bosse B, Leyendecker P, Hopp M. A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efficacy of oxycodone/naloxone prolonged-release tablets in patients with moderate/severe, chronic cancer pain. Palliat Med. 2012;26:50–60. doi:10.1177/0269216311418869. Recent and only available RCT assessing efficacy and safety of combined proglonged release oxycodone/naloxone in cancer patients.PubMedCrossRefGoogle Scholar
  17. 17.
    Reimer K, Hopp M, Zenz M, Maier C, Holzer P, Mikus G, et al. Meeting the challenges of opioid-induced constipation in chronic pain management - a novel approach. Pharmacology. 2009;83:10–7. doi:10.1159/000165778.PubMedCrossRefGoogle Scholar
  18. 18.
    Choi YS, Billings JA. Opioid antagonists: a review of their role in palliative care, focusing on use in opioid-related constipation. J Pain Symptom Man. 2002;24:71–90.CrossRefGoogle Scholar
  19. 19.
    Reid CM, Martin RM, Sterne JA, Davies AN, Hanks GW. Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166:837–43. doi:10.1001/archinte.166.8.837.PubMedCrossRefGoogle Scholar
  20. 20.
    Kalso E. Oxycodone. J Pain Symptom Man. 2005;29(5 Suppl):S47–56.CrossRefGoogle Scholar
  21. 21.
    Simpson K, Leyendecker P, Hopp M, Muller-Lissner S, Lowenstein O, De Andres J, et al. Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain. Curr Med Res Opin. 2008;24:3503–12. doi:10.1185/03007990802584454.PubMedCrossRefGoogle Scholar
  22. 22.
    Lowenstein O, Leyendecker P, Hopp M, Schutter U, Rogers PD, Uhl R, et al. Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomized controlled trial. Expert Opin Pharmacother. 2009;10:531–43. doi:10.1517/14656560902796798.PubMedCrossRefGoogle Scholar
  23. 23.
    Lowenstein O, Leyendecker P, Lux EA, Blagden M, Simpson KH, Hopp M, et al. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of 2 randomized, double-blind clinical trials. BMC Clin Pharmacol. 2010;10:12. doi:10.1186/1472-6904-10-12.PubMedCrossRefGoogle Scholar
  24. 24.
    Smith K, Hopp M, Mundin G, Bond S, Bailey P, Woodward J, et al. Low absolute bioavailability of oral naloxone in healthy subjects. Int J Clin Pharmacol Ther. 2012;50:360–7.PubMedGoogle Scholar
  25. 25.
    Lotsch J, Walter C, Parnham MJ, Oertel BG, Geisslinger G. Pharmacokinetics of non-intravenous formulations of fentanyl. Clin Pharmacokinet. 2012. doi:10.1007/s40262-012-0016-7.
  26. 26.
    Zeppetella G. Opioids for the management of breakthrough cancer pain in adults: a systematic review undertaken as part of an EPCRC opioid guidelines project. Palliat Med. 2011;25:516–24. doi:10.1177/0269216310385601.PubMedCrossRefGoogle Scholar
  27. 27.
    • Schneider G, Voltz R, Gaertner J. Cancer pain management and bone metastases: an update for the clinician. Breast Care. 2012;7:113–20. doi:10.1159/000338579. Short and pragmatic tutorial for clinicians who are not palliative care or pain specialist.PubMedCrossRefGoogle Scholar
  28. 28.
    •• Bennett MI, Graham J, Schmidt-Hansen M, Prettyjohns M, Arnold S. Prescribing strong opioids for pain in adult palliative care: summary of NICE guidance. BMJ. 2012;344:e2806. doi:10.1136/bmj.e2806. Easy to read, concise summary of current NICE Guidelines for opioid therapy.PubMedCrossRefGoogle Scholar
  29. 29.
    • 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 Oncol. 2012;13:e58–68. doi:10.1016/S1470-2045(12)70040-2. Recently released guidelines from the European Association of Palliative Care (EAPC).PubMedCrossRefGoogle Scholar
  30. 30.
    McNicol E, Horowicz-Mehler N, Fisk RA, Bennett K, Gialeli-Goudas M, Chew PW, et al. Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review. Pain. 2003;4:231–56.Google Scholar
  31. 31.
    Fallon M, McConnell S. The principles of cancer pain management. Clin Med. 2006;6:136–9.PubMedGoogle Scholar
  32. 32.
    Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. Pain. 2012;13:438–49. doi:10.1016/j.jpain.2012.01.003.CrossRefGoogle Scholar
  33. 33.
    Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147 Suppl 1:S163–71. doi:10.1038/sj.bjp.0706406.PubMedGoogle Scholar
  34. 34.
    Welch SP, Stevens DL. Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. J Pharmacol Exp Ther. 1992;262:10–8.PubMedGoogle Scholar
  35. 35.
    Kerr C, Holahan T, Milch R. The use of ketamine in severe cases of refractory pain syndromes in the palliative care setting: a case series. J Palliat Med. 2011;14:1074–7. doi:10.1089/jpm.2010.0424.PubMedCrossRefGoogle Scholar
  36. 36.
    Quibell R, Prommer EE, Mihalyo M, Twycross R, Wilcock A. Ketamine. J Pain Symptom Man. 2011;41:640–9. doi:10.1016/j.jpainsymman.2011.01.001.CrossRefGoogle Scholar
  37. 37.
    Middela S, Pearce I. Ketamine-induced vesicopathy: a literature review. Int J Clin Pract. 2011;65:27–30. doi:10.1111/j.1742-1241.2010.02502.x.PubMedCrossRefGoogle Scholar
  38. 38.
    • Hardy J, Quinn S, Fazekas B, Plummer J, Eckermann S, Agar M, et al. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. J Clin Oncol. 2012;30:3611–7. doi:10.1200/jco.2012.42.1081. Recent and sophisticated RCT about efficacy and safety of ketamine for cancer pain.PubMedCrossRefGoogle Scholar
  39. 39.
    Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, et al. Randomized, double-blind study of denosumab vs zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29:1125–32. doi:10.1200/jco.2010.31.3304.PubMedCrossRefGoogle Scholar
  40. 40.
    Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, et al. Denosumab vs zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomized, double-blind study. Lancet. 2011;377:813–22. doi:10.1016/s0140-6736(10)62344-6.PubMedCrossRefGoogle Scholar
  41. 41.
    Cleeland CS, Body JJ, Stopeck A, von Moos R, Fallowfield L, Mathias SD, et al. Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid. Cancer. 2012. doi:10.1002/cncr.27789.
  42. 42.
    Van Poznak CH, Temin S, Yee GC, Janjan NA, Barlow WE, Biermann JS, et al. American society of clinical oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol. 2011;29:1221–7. doi:10.1200/jco.2010.32.5209.PubMedCrossRefGoogle Scholar
  43. 43.
    Garcia de Paredes ML, del Moral GF, Martinez del Prado P, Marti Ciriquian JL, Enrech Frances S, Cobo Dols M, et al. First evidence of oncologic neuropathic pain prevalence after screening 8615 cancer patients. Results of the on study. Ann Oncol. 2011;22:924–30. doi:10.1093/annonc/mdq449.PubMedCrossRefGoogle Scholar
  44. 44.
    Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomized, phase 3 trials. Eur J Cancer. 2012;48:3082–92. doi:10.1016/j.ejca.2012.08.002.PubMedCrossRefGoogle Scholar
  45. 45.
    Allard P, Maunsell E, Labbe J, Dorval M. Educational interventions to improve cancer pain control: a systematic review. J Palliat Med. 2001;4:191–203.PubMedCrossRefGoogle Scholar
  46. 46.
    Wool MS, Mor V. A multidimensional model for understanding cancer pain. Cancer Invest. 2005;23:727–34. doi:10.1080/07357900500360032.PubMedCrossRefGoogle Scholar
  47. 47.
    Ong CK, Forbes D. Embracing Cicely Saunders’s concept of total pain. BMJ. 2005;331:576. doi:10.1136/bmj.331.7516.576-d.PubMedCrossRefGoogle Scholar
  48. 48.
    Chochinov HM, Hack T, Hassard T, Kristjanson LJ, McClement S, Harlos M. Dignity in the terminally ill: a cross-sectional, cohort study. Lancet. 2002;360:2026–30. doi:10.1016/s0140-6736(02)12022-8.PubMedCrossRefGoogle Scholar
  49. 49.
    Rustoen T, Valeberg BT, Kolstad E, Wist E, Paul S, Miaskowski C. The PRO-SELF(©) pain control program improves patients’ knowledge of cancer pain management. J Pain Symptom Man. 2012;44:321–30. doi:10.1016/j.jpainsymman.2011.09.015.CrossRefGoogle Scholar
  50. 50.
    Miaskowski C, Cleary J, Burney R, Coyne P, Finley R, Foster R. Guideline for the management of cancer pain in adults and children. Glenview: American Pain Society; 2004.Google Scholar
  51. 51.
    Gordon D, Dahl J, Miaskowski C, McCarberg B, Todd K, Paice J, et al. American pain society recommendations for improving the quality of acute and cancer pain management: American pain society quality of care task force. Arch Intern Med. 2005;165:1574–80.PubMedCrossRefGoogle Scholar
  52. 52.
    Bennett MI, Bagnall AM, Jose CS. How effective are patient-based educational interventions in the management of cancer pain? systematic review and meta-analysis. Pain. 2009;143:192–9. doi:10.1016/j.pain.2009.01.016.PubMedCrossRefGoogle Scholar
  53. 53.
    • Sheinfeld Gorin S, Krebs P, Badr H, Janke EA, Jim HS, Spring B, et al. Meta-analysis of psychosocial interventions to reduce pain in patients with cancer. J Clin Oncol. 2012;30:539–47. doi:10.1200/jco.2011.37.0437. Recent meta-analysis of the effect of psychosocial interventions to reduce cancer pain.PubMedCrossRefGoogle Scholar
  54. 54.
    •• Smith TJ, Temin S, Alesi ER, Abernethy AP, Balboni TA, Basch EM, et al. American society of clinical oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol. 2012;30:880–7. Current ASCO recommendation fo the integration of palliative care into cancer care.PubMedCrossRefGoogle Scholar
  55. 55.
    Koyyalagunta D, Bruera E, Solanki DR, Nouri KH, Burton AW, Toro MP, et al. A systematic review of randomized trials on the effectiveness of opioids for cancer pain. Pain Physician. 2012;15(3 Suppl):ES39–58.PubMedGoogle Scholar
  56. 56.
    Portenoy RK. Treatment of cancer pain. Lancet. 2011;377:2236–47. doi:10.1016/s0140-6736(11)60236-5.PubMedCrossRefGoogle Scholar
  57. 57.
    Higginson IJ, Evans CJ. What is the evidence that palliative care teams improve outcomes for cancer patients and their families? Cancer J. 2010;16:423–35. doi:10.1097/PPO.0b013e3181f684e5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Palliative CareUniversity Hospital CologneCologneGermany
  2. 2.Center for Integrated OncologyUniversity HospitalCologne/BonnGermany
  3. 3.Clinical Trials Center Cologne BMBF 01KN0706CologneGermany

Personalised recommendations