Intervention Review

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Oral morphine for cancer pain

  1. Philip J Wiffen1,*,
  2. Bee Wee2,
  3. R Andrew Moore1

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 23 JUL 2013

Assessed as up-to-date: 10 JUL 2013

DOI: 10.1002/14651858.CD003868.pub3


How to Cite

Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD003868. DOI: 10.1002/14651858.CD003868.pub3.

Author Information

  1. 1

    University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences, Oxford, Oxfordshire, UK

  2. 2

    Churchill Hospital, Nuffield Department of Medicine and Sir Michael Sobell House, Oxford, UK

*Philip J Wiffen, Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. phil.wiffen@ndcn.ox.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 23 JUL 2013

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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
Ahmedzai 1997 {published data only}
Arkinstall 1989 {published data only}
  • Arkinstall WW, Goughnour BR, White JA, Stewart JH. Control of severe pain with sustained-release morphine tablets versus oral morphine solution. Canadian Medical Association Journal 1989;140(6):653-7.
  • Goughnour BR, Arkinstall WW, Stewart JH. Analgesic response to single and multiple doses of controlled release morphine tablets and morphine oral solution in cancer patients. Cancer 1989;63(Suppl 11):2294-7.
Babul 1998 {published data only}
  • Babul N, Provencher L, Laberge F, Harsanyi Z, Moulin D. Comparative efficacy and safety of controlled-release morphine suppositories and tablets in cancer pain. Journal of Clinical Pharmacology 1998;38(1):74-81.
Boureau 1992 {published data only}
  • Boureau F, Saudubray F, D'Arnoux C, Vedrenne J, Estève M, Roquefeuil B, et al. A comparative study of controlled-release morphine (CRM) suspension and CRM tablets in chronic cancer pain. Journal of Pain and Symptom Management 1992;7(7):393-9.
Broomhead 1997a {published data only}
  • Broomhead A, Kerr R, Tester W, O'Meara P, Maccarrone C, Bowles R, et al. Comparison of a once-a-day sustained-release morphine formulation with standard oral morphine treatment for cancer pain. Journal of Pain and Symptom Management 1997;14(2):63-73.
Bruera 1998 {published data only}
  • Bruera E, Belzile M, Pituskin E, Fainsinger R, Darke A, Harsanyi Z, et al. Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. Journal of Clinical Oncology 1998;16(10):3222-9.
Bruera 2004 {published data only}
  • Bruera E, Palmer JL, Bosnjak S, Rico MA, Moyano J, Sweeney C, et al. Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study. Journal of Clinical Oncology 2004;22(1):185-92.
Cundiff 1989 {published data only}
  • Cundiff D, McCarthy K, Savarese JJ, Kaiko R, Thomas G, Grandy R, et al. Evaluation of a cancer pain model for the testing of long-acting analgesics. The effect of MS Contin in a double-blind, randomized crossover design. Cancer 1989;63(11 Suppl):2355-9.
  • Cundiff D, Savarese J, Grandy R, MacCarthy K, R. Kaiko R, G. Thomas G, et al. Evaluation of a controlled- and immediate release morphine and a unique well-controlled study design in cancer pain. Journal of Pain and Symptom Management 1988;3((Suppl)):18.
Currow 2007 {published data only}
  • Currow DC, Plummer JL, Cooney NJ, Gorman D, Glare PA. A randomized, double-blind, multi-site, crossover, placebo-controlled equivalence study of morning versus evening once-daily sustained-release morphine sulfate in people with pain from advanced cancer. Journal of Pain and Symptom Management 2007;34:17-23.
Dale 2009 {published data only}
  • Dale O, Piribauer M, Kaasa S, Moksnes K, Knobel H, Klepstad P. A double-blind, randomized, crossover comparison between single-dose and double-dose immediate-release oral morphine at bedtime in cancer patients. Journal of Pain and Symptom Management 2009;37:68-76.
De Conno 1995 {published data only}
  • De Conno F, Ripamonti C, Saita L, MacEachern T, Hanson J, Bruera E. Role of rectal route in treating cancer pain: a randomized crossover clinical trial of oral versus rectal morphine administration in opioid-naive cancer patients with pain. Journal of Clinical Oncology 1995;13(4):1004-8.
Dellemijn 1994 {published data only}
  • Dellemijn PL, Verbiest HB, Van Vliet JJ, Roos PJ, Vecht CJ. Medical therapy of malignant nerve pain. A randomised double-blind explanatory trial with naproxen versus slow-release morphine. European Journal of Cancer 1994;30A(9):1244-50.
Deschamps 1992 {published data only}
  • Deschamps M, Band PR, Hislop TG, Rusthoven J, Iscoe N, Warr D. The evaluation of analgesic effects in cancer patients as exemplified by a double-blind, crossover study of immediate-release versus controlled-release morphine. Journal of Pain and Symptom Management 1992;7(7):384-92.
Ferrell 1989 {published data only}
  • Ferrell B, Wisdom C, Wenzl C, Brown J. Effects of controlled released morphine on quality of life for cancer pain. Oncology Nursing Forum 1989;16(4):521-6.
Finn 1993 {published data only}
  • Finn JW, Walsh TD, MacDonald N, Bruera E, Krebs LU, Shepard KV. Placebo-blinded study of morphine sulfate sustained-release tablets and immediate-release morphine sulfate solution in outpatients with chronic pain due to advanced cancer. Journal of Clinical Oncology 1993;11(5):967-72.
Flöter 1997 {published data only}
  • Flöter T, Koch EMW, and the Kap-Cas study group. Comparison of two oral morphine formulations for chronic severe pain of malignant and non malignant origin Kapanol (R) vs MST (R). Clinical Drug Investigation 1997;14(3):183-91.
Gillette 1997 {published data only}
  • Gillette JF, Ferme C, Moisy N, Mignot L, Schach R, Vignaux J, et al. Double-blind crossover clinical and pharmacokinetic comparison of oral morphine syrup and sustained release morphine sulfate capsules in patients with cancer-related pain. Clinical Drug Investigation 1997;14(Suppl 1):22-7.
Gourlay 1997 {published data only}
  • Gourlay GK, Cherry DA, Onley MM, Tordoff SG, Conn DA, Hood GM, et al. Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the treatment of severe cancer pain. Pain 1997;69(3):295-302.
Guo-Zhu 1997 {published data only}
  • Guo-Zhu Xu, Zhi-Ji Cai, Yan-Ping Deng, Jun Hou, Guang-Ru Xie, Shu-Jun Liu. Clinical Evaluation of the analgesic effect of sustained release morphine sulfate microgranules in patients with terminal cancer. Clinical Drug Investigation 1997;Suppl: 14(1):34-42.
Hagen 2005 {published data only}
  • Hagen NA, Thirlwell M, Eisenhoffer J, Quiqley P, Harsanyi Z, Darke A. Efficacy, safety, and steady state pharmacokinetics of once-a -day controlled release morphine (MS Contin XL) in cancer pain. Journal of Pain and Symptom Management 2005;29(1):80-90.
Hanks 1987a {published data only}
Hanks 1995 {published data only}
  • Hanks GW, Hanna M, Finlay I, Radstone DJ, Keeble T. Efficacy and pharmacokinetics of a new controlled-release morphine sulfate 200-mg tablet. Journal of Pain and Symptom Management 1995;10(1):6-12.
Hanna 2008 {published data only}
  • Hanna M, Thipphawong J. A randomized, double-blind comparison of OROS hydromorphone and controlled-release morphine for the control of chronic cancer pain. BMC Palliative Care 2008;7:17.
Harris 2003 {published data only}
Heiskanen 2000 {published data only}
Homsi 2010 {published data only}
  • Homsi J, Walsh D, Lasheen W, Nelson K A, Rybicki L A, Bast J, et al. A comparative study of 2 sustained-release morphine preparations for pain in advanced cancer. American Journal of Hospice and Palliative Care 2010;27:99-105.
Hoskin 1989 {published data only}
Kalso 1990 {published data only}
  • Kalso E, Vainio A. Morphine and oxycodone hydrochloride in the management of cancer pain. Clinical Pharmacology and Therapeutics 1990;47(5):639-46.
Kerr 2000 {published data only}
  • Kerr RO, Tester WJ. A patient preference study comparing two extended-release morphine sulfate formulations (once-daily Kadian™ versus twice-daily MS Contin™ for cancer pain. Clinical Drug Investigation 2000;19(1):25-32.
Klepstad 2003 {published data only}
  • Klepstad P, Kaasa S, Jystad A, Hval B, Borchgrevink PC. Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trial. Pain 2003;101(1-2):193-8.
Knudsen 1985 {published data only}
  • Henriksen H, Knudsen J. Controlled evaluation and ongoing experience with sustained release morphine in patients with advanced cancer pain. Advances in Cancer Pain Management. The International Symposium on Pain Control. Toronto: Purdue Frederick Inc, 1986.
  • Knudsen J, Mortensen SM, Eikard B, Henriksen H. Slow-release morphine tablets compared with conventional morphine tablets in the treatment of cancer pain [Morfin-depottabletter og konventionelle morfintabletter ved cancersmerter]. Ugeskr Læger 1985;147(9):780-4.
Kossman 1983 {published data only}
  • Kossman B, Dick W, Bowdler I, Kilian J, Hecht M. Modern aspects of morphine therapy. Advances in Morphine Therapy. The 1983 International Symposium on Pain Control. Royal Society of Medicine International Congress and Symposium Series no 64. London: Royal Society of Medicine, 1983:73-81.
Lauretti 2003 {published data only}
Leppart 2001 {published data only}
  • Leppart W. Analgesic efficacy and side effects of oral tramadol and morphine administered orally in the treatment of cancer pain. Nowotwory 2001;51(3):257-66.
Melzack 1979 {published data only}
  • Melzack R, Mount BM, Gordon JM. The Brompton mixture versus morphine solution given orally: effects on pain. Canadian Medical Association Journal 1979;120(4):435-8.
Mercadante 1998 {published data only}
  • Mercadante S, Salvaggio L, Dardanoni G, Agnello A, Garofalo S. Dextropropoxyphene versus morphine in opioid-naive cancer patients with pain. Journal of Pain and Symptom Management 1998;15(2):76-81.
Mercadante 2008 {published data only}
Mercadante 2010 {published data only}
  • Mercadante S, Tirelli W, David F, Arcara C, Fulfaro F, Casuccio A, et al. Morphine versus oxycodone in pancreatic cancer pain: a randomized controlled study. Clinical Journal of Pain 2010;26(9):294-7.
Mignault 1995 {published data only}
  • Mignault GG, Latreille J, Viguie F, Richer P, Lemire F, Harsanyi Z, et al. Control of cancer-related pain with MS Contin: a comparison between 12-hourly and 8-hourly administration. Journal of Pain and Symptom Management 1995;10(6):416-22.
Mizuguchi 1990 {published data only}
  • Mizuguchi K, Takeda F, Hiraga K, Nakashima M. Utility evaluation of morphine hydrocloride suppository, AN-631, in the treatment of cancer pain. Rinshou Igaku 1990;6(11):2357-76.
Moriarty 1999 {published data only}
  • Moriarty M, McDonald CJ, Miller AJ. A randomised crossover comparison of controlled release hydromorphone tablets with controlled release morphine tablets in patients with cancer pain. Journal of Clinical Research 1999;2:1-8.
Mucci LoRusso 1998 {published data only}
  • Mucci LoRusso P, Berman BS, Silberstein PT, Citron ML, Bressler L, Weinstein SM, et al. Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: A randomized, double-blind, parallel-group study. European Journal of Pain 1998;2:239-49.
O'Brien 1997 {published data only}
  • O'Brien T, Mortimer PG, McDonald CJ, Miller AJ. A randomized crossover study comparing the efficacy and tolerability of a novel once-daily morphine preparation (MXL capsules) with MST Continus tablets in cancer patients with severe pain. Palliative Medicine 1997;11(6):475-82.
Oztürk 2008 {published data only}
  • Oztürk T, Karadibak K, Catal D, Cakan A, Tugsavul F, Cirak K. Comparison of TD-fentanyl with sustained-release morphine in the pain treatment of patients with lung cancer [Akciğer Kanserli Hastaların Ağrılarının Tedavisinde Transdermal Fentanil ve Yavaş Salınımlı Morfinin Karşılaştırılması.]. Agri 2008;20:20-5.
Panich 1993 {published data only}
  • Panich A, Charnvej L. Comparison of morphine slow release tablet (MST) and morphine sulphate solution (MSS) in the treatment of cancer pain. Journal of Medical Association of Thailand 1993;76(12):672-6.
Portenoy 1989 {published data only}
  • Portenoy R, Maldonado M, Fitzmartin R, Kaiko R, Kanner R. Oral controlled release morphine sulfate. Analgesic efficacy and side effects of a 100 mg tablet in cancer pain patients. Cancer 1989;63(Suppl: 11):2284-8.
  • Portenoy RK, Maldonado M, Fitzmartin R, Kaiko R, Kanner R. Controlled-release morphine sulfate: analgesic efficacy and side effects of a 100 mg tablet. Journal of Pain and Symptom Management 1988;3(3):Suppl: 16.
Ridgway 2010 {published data only}
  • Ridgway D, Sopata M, Burneckis A, Jespersen L, Andersen C. Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory crossover study. Journal of Pain and Symptom Management 2010;39:712-20.
Rodriguez 1994 {published data only}
  • Rodriguez M, Barutell C, Rull M, Gálvez R, Pállares J, Vidal F, et al. Efficacy and tolerance of oral dipyrone versus oral morphine for cancer pain. European Journal of Cancer 1994;30A(5):584-7.
Smith 1991 {published data only}
  • Smith KJ, Miller AJ, McKellar J, Court M. Morphine at gramme doses: kinetics, dynamics and clinical need. Postgraduate Medical Journal 1991;67(Suppl 2):S55-9.
Thirlwell 1989 {published data only}
  • Thirlwell MP, Sloan PA, Maroun JA, Boos GJ, Besner JG, Stewart JH, et al. Pharmacokinetics and clinical efficacy of oral morphine solution and controlled-release morphine tablets in cancer patients. Cancer 1989;63(Suppl 11):2275-83.
Todd 2002 {published data only}
  • Todd J, Rees E, Gwilliam B, Davies A. An assessment of the efficacy and tolerability of a 'double dose' of normal-release morphine sulphate at bedtime.. Palliative Medicine 2002;16:507-12.
Twycross 1977 {published data only}
Vainio 1988 {published data only}
  • Vainio A, Tigerstedt I. Opioid treatment for radiating cancer pain: oral administration vs. epidural techniques. Acta Anaesthesiologica Scandinavica 1988;32(3):179-85.
Van Seventer 2003 {published data only}
  • Van Seventer R, Smit JM, Schipper RM, Wicks MA, Zuurmond WW. Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment of patients not using opioids for mild-to-moderate pain. Current Medical Research and Opinion 2003;19(6):457-69.
Ventafridda 1986 {published data only}
  • Ventafridda V, Ripamonti C, Bianchi M, Sbanotto A, De Conno F. A randomized study on oral administration of morphine and methadone in the treatment of cancer pain. Journal of Pain and Symptom Management 1986;1(4):203-7.
Ventafridda 1989 {published data only}
  • Ventafridda V, Saita L, Barletta L, Sbanotto A, De Conno F. Clinical observations on controlled release morphine in cancer pain. Journal of Pain and Symptom Management 1989;4(3):124-9.
Vielvoye-Kerkmeer 2002 {published data only}
  • Vielvoye-Kerkmeer A, Van Tinteren H, Mattern C, Schüller J, Farnell A. Sustained release morphine in cancer pain. European Journal of Palliative Care 2002;9(4):137-40.
Walsh 1985a {published data only}
  • Walsh TD. A controlled study of MST Continus tablets for chronic pain in advanced cancer. In: Wilkes E editor(s). Advances in Morphine Therapy: International Symposium on Pain Control. London: Royal Society of Medicine, 1984:99-102.
  • Walsh TD. Clinical evaluation of slow release morphine tablets. Advances in Pain Research and Therapy 1985;9:727-31.
Walsh 1992 {published data only}
  • Walsh TD, MacDonald N, Bruera E, Shepard KV, Michaud M, Zanes R. A controlled study of sustained-release morphine sulfate tablets in chronic pain from advanced cancer. American Journal of Clinical Oncology 1992;15(3):268-72.
Wilder-Smith1994 {published data only}
  • Wilder-Smith CH, Schimke J, Osterwalder B, Senn HJ. Oral tramadol, a mu-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain. Annals of Oncology 1994;5(2):141-6.
Wilkinson 1992 {published data only}
  • Wilkinson TJ, Robinson BA, Begg EJ, Duffull SB, Ravenscroft PJ, Schneider JJ. Pharmacokinetics and efficacy of rectal versus oral sustained-release morphine in cancer patients. Cancer Chemotherapy and Pharmacology 1992;31(3):251-4.
Wong 1997 {published data only}
  • Wong JO, Chiu GL, Tsao CJ, Chang CL. Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain. Acta Anaesthesiologica Sinica 1997;35(1):25-32.

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
Babul 1992 {published data only}
Beaver 1977 {published data only}
  • Beaver WT, Wallenstein SL, Houde RW, Rogers A. Comparisons of the analgesic effects of oral and intramuscular oxymorphone and of intramuscular oxymorphone and morphine in patients with cancer. Journal of Clinical Pharmacology 1977;17(4):186-98.
Beaver 1978 {published data only}
  • Beaver WT, Wallenstein SL, Rogers A, Houde RW. Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone. Journal of Pharmacology and Experimental Therapeutics 1978;207(1):92-100.
Bosek 1994 {published data only}
Brooks 1989 {published data only}
  • Brooks I, De Jager R, Blumenreich M, George E, Savarese JJ. Principles of cancer pain management. Use of long-acting oral morphine. Journal of Family Practice 1989;28(3):275-80.
Broomhead 1997b {published data only}
  • Broomhead A, West R, Kadirgamanathan G, Knox K, Krueger D, Malick J. Comparative bioavailability of sustained-release morphine sulfate capsules versus pellets. Clinical Drug Investigation 1997;14(2):137-45.
Bruera 1995 {published data only}
  • Bruera E, Fainsinger R, Spachynski K, Babul N, Harsanyi Z, Darke AC. Clinical efficacy and safety of a novel controlled-release morphine suppository and subcutaneous morphine in cancer pain: a randomized evaluation. Journal of Clinical Oncology 1995;13(6):1520-7.
Buxton 1987 {published data only}
  • Buxton B. A comparison of morphine sulphate solution and MST Continus tablets in the treatment of pain in terminally ill at home. In: Derek Doyle editor(s). International Symposium on Pain Control. Royal Society of Medicines Services International Congress and Symposium Series 123. London: Royal Society of Medicines Services Ltd, 1987:132.
Carlson 1990 {published data only}
  • Carlson RW, Borrison RA, Sher HB, Eisenberg PD, Mowry PA, Wolin EM. A multiinstitutional evaluation of the analgesic efficacy and safety of ketorolac tromethamine, acetaminophen plus codeine, and placebo in cancer pain. Pharmacotherapy 1990;10(3):211-6.
Cherny 1994 {published data only}
  • Cherny NI, Thaler HT, Friedlander-Klar H, Lapin J, Foley KM, Houde R, et al. Opioid responsiveness of cancer pain syndromes caused by neuropathic or nociceptive mechanisms: a combined analysis of controlled, single-dose studies. Neurology 1994;44(5):857-61.
Chrubasik 1987 {published data only}
  • Chrubasik J, Geller E, Niv D, Zindler M. Morphine inhalation versus intravenous infusion in pain treatment after abdominal surgery. Anesthesia and Analgesia 1987;66:Suppl: 29.
Citron 1992 {published data only}
  • Citron ML, Kalra JM, Seltzer VL, Chen S, Hoffman M, Walczak MB. Patient-controlled analgesia for cancer pain: a long-term study of inpatient and outpatient use. Cancer Investigation 1992;10(5):335-41.
Cleeland 1996 {published data only}
  • Cleeland CS, Nakamura Y, Howland EW, Morgan NR, Edwards KR, Backonja M. Effects of oral morphine on cold pressor tolerance time and neuropsychological performance. Neuropsychopharmacology 1996;15(3):252-62.
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). Pain 2001;91(1-2):123-30.
  • Coluzzi PH, Schwartzberg L, Conroy Jr JD, Charapata S, Gay M, Busch M, 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 Jr JD, Charapata S, Gay M, Busch M, et al. Irruptive pain in cancer: A randomized comparative trial of oral transmucosal fentanyl citrate (OTFC) versus immediate-release morphine sulphate (MSIR). Revista De La Sociedad Espanola Del Dolor 2002;9(5):306-16.
Cowen 1997 {published data only}
  • Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M, Faucher C, et al. Low energy helium-neon laser in the prevention of oral mucositis in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. International Journal of Radiation Oncology, Biology, Physics 1997;38(4):697-703.
Davis 1993 {published data only}
  • Davis T, Miser AW, Loprinzi CL, Kaur JS, Burnham NL, Dose AM, et al. Comparative morphine pharmacokinetics following sublingual, intramuscular, and oral administration in patients with cancer. Hospice Journal 1993;9(1):85-90.
De Bernardi 1997 {published data only}
  • De Bernardi M, De Bernardi F, Colombo P. Randomised crossover comparison of the pharmacokinetic profiles of two sustained release morphine sulfate formulations in patients with cancer-related pain. Clinical Drug Investigation 1997;14(Suppl 1):28-33.
De Conno 1997 {published data only}
  • De Conno F. Analgesic efficacy and side effects of opioids in different routes of administration for terminal cancer patients: A clinical, pharmacokinetic and neurophysiological study. Journal of Clinical Oncology 1997;13:49-51.
Deng 1997 {published data only}
  • Deng Y, Xu G, Wang K. The steady-state concentration of morphine sulphate tablets and its clinical analgesic effect in cancer patients. Chinese Pharmaceutical Journal 1997;32(6):356-9.
Donner 1998 {published data only}
Drexel 1989 {published data only}
Du 1999 {published data only}
  • Du X, Skopp G, Aderjan R. The influence of the route of administration: a comparative study at steady state of oral sustained release morphine and morphine sulfate suppositories. Therapeutic Drug Monitoring 1999;21(2):208-14.
Dudgeon 2007 {published data only}
  • Dudgeon D J, Bruera E, Gagnon B, Watanabe S M, Allan S J, Warr D G, et al. A phase III randomized, double-blind, placebo-controlled study evaluating dextromethorphan plus slow-release morphine for chronic cancer pain relief in terminally ill patients. Journal of Pain and Symptom Management 2007;33:365-71.
Ernst 1992 {published data only}
  • Ernst DS, MacDonald RN, Paterson AH, Jensen J, Brasher P, Bruera E. A double-blind, crossover trial of intravenous clodronate in metastatic bone pain. Journal of Pain and Symptom Management 1992;7(1):4-11.
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.
Faura 1996 {published data only}
  • Faura CC, Moore RA, Horga JF, Hand CW, McQuay HJ. Morphine and morphine-6-glucuronide plasma concentrations and effect in cancer pain. Journal of Pain and Symptom Management 1996;11(2):95-102.
Forman 1993 {published data only}
  • Forman WB, Portenoy RK, Yanagihara RH, Hunt C, Kush R, Shepard K. A novel morphine sulphate preparation: clinical trial of a controlled-release morphine suspension in cancer pain. Palliative Medicine 1993;7(4):301-6.
Georgiou 2000 {published data only}
  • Georgiou L, Louizos A, Sklavou C, Manolopoulos L, Yiotakis I, Adamopoulos G. Cervical versus thoracic epidural morphine for the treatment of head and neck cancer pain. Annals of Otology, Rhinology & Laryngology 2000;109(7):676-8.
Glare 1993 {published data only}
Gourlay 1986 {published data only}
  • Gourlay GK, Cherry DA, Cousins MJ. A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. Pain 1986;25(3):297-312.
Gourlay 1995 {published data only}
Griffith 1990 {published data only}
  • Griffith S, Dewberry HM, Titcombe JM, McNamara PJG, Harcourt JMV, Twycross RG. Evaluation of the palatability of Oramorph - a proprietary preparation of oral morphine sulphate. Palliative Medicine 1990;4:205-9.
Hagen 1995 {published data only}
  • Hagen N, Thirlwell MP, Dhaliwal HS, Babul N, Harsanyi Z, Darke AC. Steady-state pharmacokinetics of hydromorphone and hydromorphone-3-glucuronide in cancer patients after immediate and controlled-release hydromorphone. Journal of Clinical Pharmacology 1995;35(1):37-44.
Hanks 1984 {published data only}
  • Hanks GW, Trueman T. Controlled release morphine tablets in chronic cancer pain. Pain 1984;Suppl:406.
Hasselstrom 1991 {published data only}
  • Hasselstrom J, Alexander N, Bringel C, Svensson JO, Sawe J. Single dose and steady state kinetics of morphine and its metabolites in cancer patients - a comparison of two oral formulations. European Journal of Clinical Pharmacology 1991;40(6):585-91.
Hill 1990 {published data only}
Hill 1992 {published data only}
Hoffman 1997 {published data only}
  • Hoffman M, Xu JC, Smith C, Fanelli C, Pascal V, Degaetano C, et al. A pharmacodynamic study of morphine and its glucuronide metabolites after single morphine dosing in cancer patients with pain. Cancer Investigation 1997;15(6):542-7.
Houde 1981 {published data only}
  • Houde RW, Kaiko RF, Wallenstein SL, Rogers AG. Analgesic assay of oral zomepirac and intramuscular morphine in advanced cancer patients. Pain 1981;Suppl:247.
Kaiko 1979 {published data only}
  • Kaiko R, Wallenstein S, Rogers A, Heidrich G 3rd, Houde R. Relative analgesic potency of intramuscular heroin and morphine in cancer patients with postoperative pain: a preliminary report. National Institute on Drug Abuse Research Monograph 1979;27:254-60.
Kaiko 1984 {published data only}
  • Kaiko RF, Wallenstein SL, Lapin J, Houde RW. Oral fenoprofen compared to intramuscular morphine and oral aspirin in cancer patients with postoperative pain. National Institute on Drug Abuse Research Monograph 1984;49:205-11.
Kaiko 1987 {published data only}
Kaiko 1989 {published data only}
  • Kaiko RF, Grandy RP, Oshlack B, Pav J, Horodniak J, Thomas G, et al. The United States experience with oral controlled release morphine (MS Contin tablets). Parts I and II. Review of nine dose titration studies and clinical pharmacology of 15 mg, 30 mg, 60 mg, and 100 mg tablet strengths in normal subjects. Cancer 1989;63(Suppl 11):2348-54.
Kalso 1996 {published data only}
Khojasteh 1987 {published data only}
  • Khojasteh A, Evans W, Reynolds R, Thomas G, Savarese J. Controlled release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation. Journal of Clinical Oncology 1987;5(6):956-61.
Lakdja 1997 {published data only}
  • Lakdja F, Dixmerias F, Bussieres E, Fonrouge J-M, Lobera A. Preemptive analgesia on postmastectomy pain syndrome with ibuprofen-arginine [Effet analgesique preventif d'une administration perioperatoire d'ibuprofene-arginine sur le syndrome douloureux postmastectomie]. Bulletin Du Cancer 1997;84(3):259-63.
Lauretti 1999 {published data only}
  • Lauretti GR, Lima IC, Reis MP, Prado WA, Pereira NL. Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management. Anesthesiology 1999;90(6):1528-33.
Lazarus 1990 {published data only}
  • Lazarus H, Fitzmartin RD, Goldenheim PD. A multi investigator clinical evaluation of oral controlled release morphine (MS Contin tablets) administered to cancer patients. Hospice Journal 1990;6(4):1-15.
Li 1994 {published data only}
  • Li QS, Cao SH, Xie GM, Gan YH, Ma H, Lu JZ, et al. Combined traditional Chinese medicine and Western medicine. Relieving effects of Chinese herbs, ear-acupuncture and epidural morphine on postoperative pain in liver cancer. Chinese Medical Journal 1994;107(4):289-94.
Marinangeli 2004 {published data only}
  • Marinangeli F, Ciccozzi A, Leonardis M, Aloisio L, Mazzei A, Paladini A, et al. Use of strong opioids in advanced cancer pain: a randomized trial. Journal of Pain and Symptom Management 2004;27(5):409-16.
Masood 1995 {published data only}
  • Masood AR, Subhan MM, Reed JW, Thomas SH. Effects of inhaled nebulized morphine on ventilation and breathlessness during exercise in healthy man. Clinical Science 1995;88(4):447-52.
Masood 1996 {published data only}
Meed 1987 {published data only}
  • Meed SD, Kleinman PM, Kantor TG, Blum RH, Savarese JJ. Management of cancer pain with oral controlled-release morphine sulfate. Journal of Clinical Pharmacology 1987;27(2):155-61.
Minotti 1989 {published data only}
  • Minotti V, Patoia L, Roila F, Basurto C, Tonato M, Pasqualucci V, et al. Double-blind evaluation of analgesic efficacy of orally administered diclofenac, nefopam, and acetylsalicylic acid (ASA) plus codeine in chronic cancer pain. Pain 1989;36(2):177-83.
Minotti 1998 {published data only}
  • Minotti V, De Angelis V, Righetti E, et al. Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain. Pain 1998;74(2-3):133-7.
Morgan 1992 {published data only}
  • Morgan DJ, McCormick Y, Cosolo W, Roller L, Zalcberg J. Prolonged release of morphine alkaloid from a lipophilic suppository base in vitro and in vivo. International Journal of Clinical Pharmacology,Therapy and Toxicology 1992;30(12):576-81.
Moulin 1996 {published data only}
Penn 1992 {published data only}
Portenoy 1999a {published data only}
  • Portenoy RK, Payne R, Coluzzi P, Rashko 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.
Repas 1992 {published data only}
  • Repas C. Tramadol and the possibilities for its use with cancer patients [Tramadol i vozmozhnosti ego primeneniia u onkologicheskikh bol'nykh]. Terapevticheskii Arkhiv 1992;64(10):91-6.
Ripamonti 1992 {published data only}
  • Ripamonti C, Sita L, De Conno F, Ventafridda V, MacEachern T, Hanson J, et al. Rectal versus oral morphine for the management of cancer pain. A double-blind, double dummy cross-over trial. Proceedings of the Annual Meeting of the American Society of Clinical Oncology. ASCO, 1992:397.
Roca 1996 {published data only}
  • Roca G, Aguilar JL, Gomar C, Mazo V, Costa J, Vidal F. Nimodipine fails to enhance the analgesic effect of slow release morphine in the early phases of cancer pain treatment. Pain 1996;68:239-43.
Santillan 1998 {published data only}
  • Santillan R, Hurle MA, Armijo JA, De los Mozos R, Florez J. Nimodipine-enhanced opiate analgesia in cancer patients requiring morphine dose escalation: a double-blind, placebo-controlled study.. Pain 1998;76(1-2):17-26.
Savarese 1988 {published data only}
  • Savarese JJ, Thomas GB, Homesley H, Hill CS. Rescue factor: A design for evaluating long-acting analgesics. Clinical Pharmacology and Therapeutics 1988;43(4):376-80.
Säwe 1983 {published data only}
Schaer 1992 {published data only}
  • Schaer H, Baasch K, Prochacka K. Intrathecal morphine for postoperative pain [Intrathekales morphin fur postoperativen schmerz]. Anaesthesist 1992;41(11):689-93.
Sjogren 1989 {published data only}
  • Sjogren P, Banning AM, Henriksen H. High-dose epidural opioid treatment of malignant pain [Højdosis epidural opiodbehandling af miligne smerter]. Ugeskrift Laeger 1989;151(1):25-8.
Sloan 1998 {published data only}
Stambaugh 1981 {published data only}
  • Stambaugh JE. Comparison of the analgesic effect of parenteral levonantradol to morphine and placebo in patients with moderate to severe pain of cancer. Pain 1981;Suppl:97.
Stambaugh 1990 {published data only}
  • Stambaugh J, Drew J, Davis M. Comparison of immediate vs. sustained released oral morphine in cancer patients - acute pain novel study design. Journal of Clinical Pharmacology 1990;30:838.
Stambaugh 2001 {published data only}
  • Stambaugh JE, Reder RF, Stambaugh MD, Stambaugh H, Davis M. Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients. 41. Journal of Clinical Pharmacology 2001;41(5):500-6.
Sykes 1996 {published data only}
Takeda 1987 {published data only}
  • Takeda F. A clinical evaluation of S-8114 (morphine sulphate controlled-release tablets) in the management of cancer pain: comparison with oral morphine hydrochloride. Kiso to Rinsho (The Clinical Report) 1987;21(17):6889-906.
Tawfik 1990 {published data only}
  • Tawfik MO, Elborolossy K, Nasr F. Tramadol hydrochloride in the relief of cancer pain. A double blind comparison against sustained release morphine. Pain 1990;Suppl:S377.
Wallenstein 1980 {published data only}
  • Wallenstein SL, Rogers A, Kaiko RF, Heidrich G 3d, Houde RW. Relative analgesic potency of oral zomepirac and intramuscular morphine in cancer patients with postoperative pain. Journal of Clinical Pharmacology 1980;20(4):250-8.
Walsh 1984 {published data only}
  • Walsh TD. Controlled study of slow release morphine for chronic pain in advanced cancer. Pain 1984;Suppl:S202.
Walsh 1985b {published data only}
  • Walsh TD. Controlled study of oral slow release morphine in pain due to advanced cancer. Proceedings of the Annual Meeting of the American Society of Clinical Onclogy. Vol. 9, ASCO, 1985:Abs No 1035.
Weingart 1985 {published data only}
  • Weingart W, Sorkness C, Earhart R. Analgesia with oral narcotics and added ibuprofen in cancer patients. Clinical Pharmacy 1985;4(1):53-8.
Westerling 1993 {published data only}

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
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Collins 1998
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Faura 1998
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Moore 2010
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Nüesch 2010
Parfitt 1999
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Portenoy 1999b
Quigley 2007
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RevMan 2012
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Schmidt-Hansen 2010
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WHO 2011
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