Revista de Oncología

, Volume 6, Issue 5, pp 272–282 | Cite as

Manejo farmacológico del dolor crónico oncológico. Una aproximación actual

  • Ángel Segura HuertaEmail author
  • Roberto Díaz Beveridge
  • Verónica Calderero Aragón
  • Laura Palomar Abad


El tratamiento del dolor es una de las prioridades de la Organización Mundial de la Salud (OMS) en la lucha contral el cáncer. La OMS aboga por su escala analgésica contresniveles.

Los opioides mayores son el tratamiento farmacológico fundamental del dolor oncológico crónico. La morfina oral de liberación inmediata tiene una duración de acción de 4 horas. La morfina oral de liberación retardada tiene 8–12 horas de duración. El fentanilo transdérmico es un sistema diseñado para liberar el fármaco durante 72 horas. Hay sistemas diseñados para liberar 25, 50, 75 y 100 μg/hora, según la superficie del parche. La buprenorfina transdérmica es el último medicamento comercializado para el tratamiento del dolor crónico. Existen tres presentaciones, cada una de ellas libera de forma respectiva 35, 52,5 y 70 μg/hora. El parche debe cambiarse cada 72 horas.

La terapéutica fundamental en el manejo del dolor incidental es el uso de dosis suplementarias de opioides de liberación inmediata. La dosis oscila entre el 10%–25% de la dosis opioide total diaria.

Palabras clave

dolor crónico morfina fentanilo buprenorfina cáncer 

Management of cancer-associated chronic pain with medication: a current approximation


Treatment of pain is one of the priorities of the WHO in its fight against cancer: The WHO advocates a three-stage scale of analgesia:

The stronger opioids are the fundamental treatment of cancer-associated chronic pain. Immediate-release oral morphine has a duration of activity of 4 hours. Late-release oral morphine has an action of 8–12 hour duration. Transdermal fentanyl is a system designed to release the drug over 72 hours. There are systems designed to release 25, 50, 75 and 100 μg/h, depending of the surface area of the patch. Transdermal buprenorphine is the latest medication commercialised for the treatment of chronic pain. These are three preparations that release 35, 52.5 or 70 μg/h. The patch needs to be changed every 72 hours.

The fundamental therapy in the management of cancer-associated pain is the use of immediate-release opioid supplements. The dose can vary between 10%–25% of the total daily opioid dose.

Key words

chronic pain morphine fentanyl buprenorfine cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Report of the WHO Expert Committee on Cancer Pain Relief and Active Supportive Care. Cancer Pain Relief with a guide to opioid availability. 2nd ed. Technical Report Series, 804. Geneva: World Health Organization, 1996.Google Scholar
  2. 2.
    Foley KM. Management of cancer pain. En: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia: J. Lippincot, 1996.Google Scholar
  3. 3.
    Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. Pain 1999; 82:263–74.CrossRefGoogle Scholar
  4. 4.
    Grond S, Zech D, Diefenbach C, Bischoff A. Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation, of 1635 cancer patients referred to a pain clinic. J Pain Symptom Manage 1994;73:907–14.Google Scholar
  5. 5.
    Banning A, Sjogren P, Henriksen H. Pain causes in 200 patients referred to a multidisciplinary cancer pain clinic. Pain 1991;45:45–8.CrossRefGoogle Scholar
  6. 6.
    Cleeland CS. The impact of pain in patients with cancer. Cancer 1984;54:263.CrossRefGoogle Scholar
  7. 7.
    Kelsen DP, Portenoy RK, Thaler HT, et al. Pain and depression in patients with newly diagnosed pancreas cancer. J Clin Oncol 1995;13:748–55.CrossRefGoogle Scholar
  8. 8.
    Ferrel BR, Wisdon C, Wenzl C. Quality of life as an outcome variable in management of cancer pain. Cancer 1989;63:2621–9.Google Scholar
  9. 9.
    Cleeland CS, Gonin R, Hatfield A, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994;330:592–6.CrossRefGoogle Scholar
  10. 10.
    Von Roenn JH, Cleeland CS, Gonin R, et al. Physician attitudes and practice in cancer pain management: a survey from the Eastern Oncology Group. Ann Intern Med 1993;119:121–6.CrossRefGoogle Scholar
  11. 11.
    Ferrell BR, Dean GE, Grant M, Coluzzi P. An institutional commitmment to pain management. J Clin Oncol 1995;13:2158–65.CrossRefGoogle Scholar
  12. 12.
    Du Pen SL, Du Pen AR, Polissar N, et al. Implementing guidelines for cancer pain management: results of a randomized contolled clinical trial. J Clin Oncol 1999;17:561–70.CrossRefGoogle Scholar
  13. 13.
    Foley KM, Portenoy RK. World Health Organization/International Association for the Study of Pain: joint initiative in cancer pain treatment. J Pain Symptom Manage 1993;8:335–9.CrossRefGoogle Scholar
  14. 14.
    Jadad AR, Bowman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA 1996;274:1870–3.CrossRefGoogle Scholar
  15. 15.
    Eisenberg E, Berkey CS, Carr DB, et al. Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis. J Clin Oncol 1994;12:2756–65.CrossRefGoogle Scholar
  16. 16.
    Brooke PM, Day RO. Non-steroidal anti-inflammatory drugs-differences and similarities. N Engl J Med 1991;324:1716–25.CrossRefGoogle Scholar
  17. 17.
    Rang HP, Dale MM, Ritter JM. Anti-inflammatory and immunosupressant drugs. En: Rang HP, Dale MM, Ritter JM, editors. Pharmacology. 3rd ed. Edimburgo: Churchill-Livingstone, 1995;p. 246–66.Google Scholar
  18. 18.
    Simon LS, Weaver AL, Graham DY et al. The anti-inflammatory and upper gastrointestinal effect of celecoxib in rheumatoid arthritis: a randomized, controlled trial. JAMA 2000;82:1921–8.Google Scholar
  19. 19.
    Cannon GW, Breedveld F. Efficacy of cyclooxigenase-2-specific inhibitors. Am J Med 2001;110:6S-12S.CrossRefGoogle Scholar
  20. 20.
    Buttgereit F, Burmester GR, Simon LS. Gastrointestinal toxic side-effects of nonsteroidal anti-inflammatory drugs and cyclooxigenase-2-specific inhibitors. Am J Med 2001;110:13S-9S.CrossRefGoogle Scholar
  21. 21.
    Lipsky PE. Recommendations for the clinical use of cyclooxigenase-2-specific inhibitors. Am J Med 2001;110: 3S-5S.CrossRefGoogle Scholar
  22. 22.
    García Rodríguez LA. Non steroideal antiinflammatory drugs, ulcers and risk: a collaborative meta-anlysis. Semin Arthritis Rheum 1997;26(Suppl 1):16–20.CrossRefGoogle Scholar
  23. 23.
    Chary S, Goughnour BR, Moulin DE, et al. The doseresponse relationship of controlled-release codeine (codeine contin) in chronic cancer pain. J Pain Symptom Manage 1994;9:363–71.CrossRefGoogle Scholar
  24. 24.
    Wilder-Smith CH, Schimke J, Osterwalder B, et al. Oral tramadol, a mu-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain. Ann Oncol 1994;5:141–6.CrossRefGoogle Scholar
  25. 25.
    Sunshine A. New clinical experience with tramadol. Drugs 1994;47(Suppl 1):8–18.CrossRefGoogle Scholar
  26. 26.
    Harati Y, Gooch C, Swensen M, et al. Double-blind randomized trial of tramadol for the treatment of pain of diabetic neuropathy. Neurology 1998;50:1842–6.CrossRefGoogle Scholar
  27. 27.
    Wood AJJ. Pharmacologic treatment of cancer pain. N Engl J Med 1996;335(15):1124–31.CrossRefGoogle Scholar
  28. 28.
    Cherny NI, Portenoy RK. The management of cancer pain. CA Cancer J Clin 1994;44:263–303.CrossRefGoogle Scholar
  29. 29.
    Levy MH. Pharmacologic management of cancer pain. Semin Oncol 1994;21:718–39.PubMedGoogle Scholar
  30. 30.
    Hoskin PJ, Hanjs GW, Aherne GW, et al. The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers. Br J Clin Pharmacol 1989;27:499–505.CrossRefGoogle Scholar
  31. 31.
    Gourlay GK, Plummer JL, Cherry DA, et al. The reproducibility of bioavailability of oral morphine from solution under fed and fasted conditions. J Pain Symptom Manage 1991;6:431–6.CrossRefGoogle Scholar
  32. 32.
    Sawe J, Svensson JO, Rane A. Morphine metabolism in cancer patients on increasing oral doses—no evidence of autoinduction or dose dependence. Br J Clin Pharmacol 1983;16:85–93.CrossRefGoogle Scholar
  33. 33.
    Lehmann KA, Zech D. Morphine-6-glucuronide a pharmacologically active metabolite: a review of the literature. Eur J Pain 1993;12:28–35.Google Scholar
  34. 34.
    D'Honneur G, Gilton A, Sandouk P, et al. Plasma and cerebrospinal concentration of morphine and morphine glucuronides after oral morphine. The influence of renal failure. Anesthesiology 1994;81:87–93.CrossRefGoogle Scholar
  35. 35.
    Foley KM. The treatment of cancer pain. N Engl J Med 1985;313:84–95.CrossRefGoogle Scholar
  36. 36.
    Hanks GW. Controlled-released morphine (MST Continuous) in advanced cancer: the European experience. Cancer 1989;623:2378–82.CrossRefGoogle Scholar
  37. 37.
    Coley N, Cherny NI, Portenoy RK. Subcutaneous opioid infusions in the home. Oncology 1994;8:21–7.Google Scholar
  38. 38.
    Twycross RG. The therapeutic equivalence of oral and subcutaneous/intramuscular morphine sulphate in cancer patients. J Palliative Care 1998;2:67–8.Google Scholar
  39. 39.
    Hanning CD. The rectal absorption of opiodis. En: Benedetti C, Chapman CR, Giron G, editors. Advances in Pain Research and Therapy, vol. 14. New York: Raven Press 1990; p. 259–69.Google Scholar
  40. 40.
    Expert Working Group of the European Association for Palliative Care. Morphine in cancer pain: modes of administration. BMJ 1996;312:823–6.CrossRefGoogle Scholar
  41. 41.
    Osborne JR, Joel SP, Slevin ML. Morphine intoxication in renal failure: the role of morphine-6-glucuronide. BMJ 1986;292:1548–9.CrossRefGoogle Scholar
  42. 42.
    Portenoy RK, Foley KM, Stulman J, et al. Plasma morphine and morphine-6-glucuronide during chronic morphine therapy for cancer pain: plasma profiles, steady state concentrations and the consequences of renal failure. Pain 1991;47:13–9.CrossRefGoogle Scholar
  43. 43.
    Kaiko RF. Controlled-released morphine for cancer-related pain. The European and North American experiences. En: Foley KM, Bonica JJ, Ventafridda V, editors. Advances in pain research and therapy. Vol. 16. Second International Congress on Cancer Pain. New York: Raven Press, 1990; p. 171.Google Scholar
  44. 44.
    Portenoy RK, Hagen NA. Breakthrough pain: definition, prevalence and characteristics. Pain 1990;41:273–81.CrossRefGoogle Scholar
  45. 45.
    Ventafridda V, Spoldi E, Caraceni A, et al. The importance of continuous subcutaneous morphine administration for cancer pain control. Pain Clinic 1986;1:47.Google Scholar
  46. 46.
    Levy MH. Constipation and diarrhea in cancer patients. Cancer Bull 1991;43:412–22.Google Scholar
  47. 47.
    Bruera E, Suarez-Almazor M, Velasco A, et al. The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 1994;515–9.Google Scholar
  48. 48.
    Foley KM. Clinical tolerance to opioids. En: Towards a new farmacotherapy of pain, Dahlem Konfrenzen. Chichester: Wiley, 1991; p. 81–204.Google Scholar
  49. 49.
    Bradberry JC, Reabel MA. Continuous infusion of naloxone in the treatment of narcotic overdose. Drug Untelligence and Clinical Pharmacy 1981;15:85–90.Google Scholar
  50. 50.
    Bruera E, MacMillan K, Hanson J, MacDonald RN. The cognitive effects of the administration of narcotic analgesics in patients with cancer pain. Pain 1989;39: 13–6.CrossRefGoogle Scholar
  51. 51.
    Vainio A, Olilla J, Matikainen E, Rosenberg P, Kalso E. Driving ability in cancer patients receiving long-term morphine analgesia. Lancet 1995;346:667–70.CrossRefGoogle Scholar
  52. 52.
    Sawynok J, Yaksh TL. Caffeine as an analgesic adjuvant: a review of pharmacology and mechanisms of action. Pharmacol Review 1993;45:43–85.Google Scholar
  53. 53.
    Bruera E, Brenneis C, Paterson AH, MacDonald RN. Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer. J Pain Symptom Manage 1989;4:3–6.CrossRefGoogle Scholar
  54. 54.
    MacDonald N, Der L, Allan S, Champion P. Opioid hyper-excitability: the application of alternate opioid therapy. Pain 1993;53:353–5.CrossRefGoogle Scholar
  55. 55.
    Tiseo PJ, Thaler TH, Lapin J, et al. Morphine-6-glucuronide concentrations and opioid-related side-effects: a survey in cancer patients. Pain 1995;61:47–54.CrossRefGoogle Scholar
  56. 56.
    Kaiko RF, Foley KM, Grabinsky PY, et al. Central nervous system excitatory of meperidine in cancer patients. Ann Neurol 1983;13:180–5.CrossRefGoogle Scholar
  57. 57.
    Bruera E, Miller E, McCallion J, et al. Cognitive failure in patients with terminal cancer: a prospective study. J Pain Symptom Manage 1992;7:192–5.CrossRefGoogle Scholar
  58. 58.
    Stiefel FC, Breitbart W, Holland JC. Corticosteroids in cancer therapy: neuropsychiatric complications. Cancer Investigation 1989;7:479–91.CrossRefGoogle Scholar
  59. 59.
    Dunphy K, Finlay N, Rathbone G, Gilbert J, Hicks F. Rehydration in palliative and terminal care:-if not, why not? Palliative Medicine 1995;9:221–8.CrossRefGoogle Scholar
  60. 60.
    Sjogren P, Jensen NH, Jensen TS. Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with other opioid agonists. Pain 1994;59:313–6.CrossRefGoogle Scholar
  61. 61.
    de Stoutz ND, Bruera E, Suarez-Almazor M. Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage 1995;10:376–84.Google Scholar
  62. 62.
    Fernández F, Holmes VF, Adams F, Kavanaugh JJ. Treatment of severe refractory agitation, with a haloperidol drip. J Clin Psychiatry 1989;49:239–41.Google Scholar
  63. 63.
    Faisinberg R, Bruera E. Treatment of, delirium in a terminally ill patient. J Pain Symptom Manage 1992;7:54–6.CrossRefGoogle Scholar
  64. 64.
    Simmonds MA, Richenbacher J. Transdermal fentanyl: long-term analgesic studies. J Pain Symptom Manage 1992;7:S36–9.CrossRefGoogle Scholar
  65. 65.
    Grond S, Zech D, Lehmann KA, Radbruch L, Breitenbach H, Hertel D. Transdermal fentanyl in the long-term treatment of cancer pain: a prospective study of 50 patients with advanced cancer of the gastrointestinal tract or the head and neck region. Pain 1997;69:191–8.CrossRefGoogle Scholar
  66. 66.
    Donner B, Zenz M, Strumpf M, Raber M. Long-term treatment of cancer pain with transdermal fentanyl. J Pain Symptom Manage 1998;15:168–75.CrossRefGoogle Scholar
  67. 67.
    Southam MA. Transdermal fentanyl therapy: system design, pharmacokinetics and efficacy. Anticancer Drugs 1996;6(Suppl 3):26–34.Google Scholar
  68. 68.
    Payne R, Chandler S, Elmhaus M. Guidelines for the clinical use of transdermal fentanyl. Anticancer Drugs 1995; 6(Suppl):S50–3.CrossRefGoogle Scholar
  69. 69.
    Varvel JR, Shafel SL, Hwang SS, Coen PA, Stanski DR. Absorption characteristics of trandermally administered fentanyl. Anesthesiology 1989;70:928–34.CrossRefGoogle Scholar
  70. 70.
    Portenoy RK, Southam MA, Gupta SK, et al. Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics. Anesthesiology 1993;78:36–43.CrossRefGoogle Scholar
  71. 71.
    Payne R, Mathias SD, Pasta DJ, Wanke LA, Williams R, Mahmoud R. Quality of life and cancer pain: satisfaction and side-effects with transdermal fentanyl versus oral morphine. J Clin Oncol 1998;16:1588–93.CrossRefGoogle Scholar
  72. 72.
    Ahmedzai S, Brooks D, the TTS-Fentanyl Cooperative Trial Group. Transdermal fentanyl versus sustained-released oral morphine in cancer pain: preference, efficacy and quality of life. J Pain Symptom Manage 1997; 13:254–61.CrossRefGoogle Scholar
  73. 73.
    Terlinden R. Pharmacokinetic study on multiple application of the buprenorphine transdermal system (TDS). 3 EFIC 2000. Nice.Google Scholar
  74. 74.
    Böhme K. Buprenorphine in a transdermal therapeutic system- a new optin. Clin Rheumatol 2002;21 (Suppl 1): S13–6.CrossRefGoogle Scholar
  75. 75.
    Kopp M. Buprenorphine transdermal system (TDS) in an open long-term study with chronic pain patients. J Pain Symptom Manage 2000;20:78.Google Scholar
  76. 76.
    Fainsinger RB, Schoeller T, Bruera E. Methadone in the management of cancer pain: a review. Pain 1993;52: 137–47.CrossRefGoogle Scholar
  77. 77.
    Ripamonti C, Zecca E, Bruera E. An update of the clinical use of methadone in cancer pain. Pain 1997;70:109–15.CrossRefGoogle Scholar
  78. 78.
    Mercadante S, Casuccio A, Agnello A, Serretta R, Calderone L, Barresi L. Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. J Clin Oncol 1998;16:3656–61.CrossRefGoogle Scholar
  79. 79.
    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;19:2898–904.CrossRefGoogle Scholar
  80. 80.
    Foley KM, Houde R. Methadone in cancer pain management: individualize dose and titrate to effect. J Clin Oncol 1998;16:3213–5.CrossRefGoogle Scholar
  81. 81.
    Bruera E, Pereira J, Watanabe S, Belzile M, Kuehn N, Hanson J. Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone and morphine. Cancer 1996; 78:852–7.CrossRefGoogle Scholar
  82. 82.
    Watanabe S, Bruera E. Corticosteroids as adjuvant analgesics. J Pain Symptom Manage 1994;9:442–5.CrossRefGoogle Scholar
  83. 83.
    Needham PR, Daley AG, Lennard RF. Steroids in advanced cancer: survey of current practice. BMJ 1992; 305:999.CrossRefGoogle Scholar
  84. 84.
    Yamada K, Ushio Y, Hayakawa T, Arita N, Yamada N, Mogami H. Effects of methylprednisolone on peritumoral brain edema. A quantitative autoradiography study. J Neurosurg 1983;59:612–9.CrossRefGoogle Scholar
  85. 85.
    Posner JB, Howieson J, Cvitkovic E. Disappearing' spinal cord compression: oncolytic effects of glucocorticoids (and other chemotherapeutic agents) on epidural metastases. Ann Neurol 1977;2:409–13.CrossRefGoogle Scholar
  86. 86.
    Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, Rider W. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol 1989;7:590–7.CrossRefGoogle Scholar
  87. 87.
    Watson CPN. Antidepressant drugs as adjuvant analgesics. J Pain Symptom Manage 1994;9:392–405.CrossRefGoogle Scholar
  88. 88.
    Sindrup SH, Gram LF, Brosen K, Eshoj O, Mogensen EF. The selective, serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symtoms. Pain 1990;42:135–44.CrossRefGoogle Scholar
  89. 89.
    Swerdlow M. Anticonvulsivant drugs and chronic pain. Clin Neuropharmacol 1984;7:51–82.CrossRefGoogle Scholar
  90. 90.
    Mellick GA, Mellicy LB, Mellick LB. Gabapentin in the management of relex sympathetic dystrophy. J Pain Symptom Manage 1995;10:265–6.CrossRefGoogle Scholar
  91. 91.
    Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999;81:129–34.CrossRefGoogle Scholar
  92. 92.
    Portenoy RK, Payne R, Coluzzi P, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study. Pain 1999;79:303–12.CrossRefGoogle Scholar
  93. 93.
    Farrar T, Cleary J, Rauck R. et al. Oral transmucosal fentanyl citrate: randomized double-blinded, placebocontrolled trial for treatment of breakthrough pain in cancer patients. J National Cancer Institute 1998;90: 611–6.CrossRefGoogle Scholar
  94. 94.
    Christie JM, Simmonds M, Patt R, et al. Dose-titration, multicenter study of oral transmucosal fentanyl citatre for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. J Clin Oncol 1998;16:3238–45.CrossRefGoogle Scholar
  95. 95.
    Streisand JB, Varvel JR, Stanski DR, et al. Absorption and bioavailability of oral transmucosal fentanyl citrate. Anesthesiology 1991;75:223–9.CrossRefGoogle Scholar
  96. 96.
    Egan TD, Sharma A, Ashburn MA, et al. Multiple dose pharmacokinetics of oral transmucosal fentanyl citrate in healthy volunteers. Anesthesiology 2000;92:665–73.CrossRefGoogle Scholar

Copyright information

© FESEO 2004

Authors and Affiliations

  • Ángel Segura Huerta
    • 1
    Email author
  • Roberto Díaz Beveridge
    • 1
  • Verónica Calderero Aragón
    • 1
  • Laura Palomar Abad
    • 1
  1. 1.Servicio de Oncología MédicaHospital Universitario La FeValencia

Personalised recommendations