Objective: Moderate to severe pain is commonly experienced by cancer and non-cancer patients. Although opioids are generally the most important drugs in chronic pain management, their use in Italy remains low. We designed a prospective open trial to assess the efficacy and safety of a standard therapy clinically available for a large range of patients.
Methods: A total of 172 consecutive patients (89 women and 83 men) with chronic pain (daily mean visual analogue scale (VAS) score > 4) that was not adequately managed by their existing pain regimen were enrolled to receive an immediate release (IR) dose of morphine: 30 mg/day (opioid-naive patients) or 60 mg/day (non-naive patients) for 5 days. After this period (start therapy), all patients were switched to slow release (SR) opioid therapy for 30 days (steady therapy). Each breakthrough pain (BTP) episode was treated with a single dose of IR morphine (20% of the daily dose) during all study periods.
Results: Daily VAS score was reduced from 7.4 ± 1.3 at baseline to 3.8 ± 1.5 (p < 0.0001) after 30 days of steady therapy in cancer and non-cancer patients. Fewer patients reported BTP events by study end (55% of patients with BTP at basal time had no BTP at last follow up), and the number of daily BTP events experienced by patients was reduced by therapy to 1–2 per day in 75% of patients reporting BTP. Further, the time delay to reach pain relief following administration of a rescue dose of IR morphine was 15 minutes or less in 52.1% of patients at study end. The standard therapy was well tolerated and fewer adverse effects were recorded at the end of the study period compared with baseline, with the exception of constipation, which showed a moderate increase (from 18.2% to 25.0%).
Conclusion: Start therapy with IR morphine followed by conversion to SR opioid therapy could be implemented as a standard therapy to manage moderate to severe chronic pain in patients with cancer or non-cancer pain. ORamorph® in TIBER study (ORTIBER).
This study received no external funding, and the authors have no potential conflicts of interest that are directly relevant. English language assistance for the preparation of this manuscript was provided by Rod McNab, Wolters Kluwer Health Medical Communications. This assistance was funded by Molteni Farmaceutici, Inc. The authors thank Ennio Sarli for data analysis.
Von Korff M, Lin EH, Fenton JJ, et al. Frequency and priority of pain patients’ health care use. Clin J Pain 2007; 23(5): 400–8CrossRefGoogle Scholar
Hanks GW, Conno F, Cherny N, et al. Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 2001; 84(5): 587–93PubMedCrossRefGoogle Scholar
Roggeri D, Saramin C, Terrazzani G, et al. Resource consumption and costs of treating pain in patients affected by cancer in a district of northeast Italy. Pharmacol Res 2007; 56(4): 329–34PubMedCrossRefGoogle Scholar
Bernabei R, Gambassi G, Lapane K, et al. Management of pain in elderly patients with cancer. SAGE Study Group. Systematic Assessment of Geriatric Drug Use via Epidemiology. JAMA. 1998; 279(23): 1877–82PubMedCrossRefGoogle Scholar
DeConno F, Ripamonti C, Fagnoni E, et al. The Merito Study: a multicenter trial of the analgesic effect and tolerability of the normal-release oral morphine during titration phase in patients with cancer pain. Palliat Med 2008; 22(3): 214–21PubMedCrossRefGoogle Scholar
Wells N, Murphy B, Douglas S, et al. Establishing the safety and efficacy of an opioid titration protocol. J Opioid Manag 2005; 1(1): 41–8PubMedGoogle Scholar
Bruera E, Pereira J, Watanabe S, et al. Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer 1996; 78(4): 852–7PubMedCrossRefGoogle Scholar
Indelicato RA, Portenoy RK. Opioid rotation in the management of refractory cancer pain. J Clin Oncol 2003; 21(9 Suppl.): 87s–91sPubMedCrossRefGoogle Scholar
Indelicato RA, Portenoy RK. Opioid rotation in the management of refractory cancer pain. J Clin Oncol 2002; 20(1): 348–52PubMedGoogle Scholar
Portenoy RK. Managing cancer pain poorly responsive to systemic opioid therapy. Oncology (Williston Park) 1999; 13(5 Suppl. 2): 25–9Google Scholar
deStoutz ND, Bruera E, Suarez-Almazor M. Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage 1995; 10(5): 378–84PubMedCrossRefGoogle Scholar
Smith HS. Variations in opioid responsiveness. Pain Physician 2008; 11(2): 237–48PubMedGoogle Scholar
Kadiev E, Patel V, Rad P, et al. Role of pharmacogenetics in variable response to drugs: focus on opioids. Expert Opin Drug Metab Toxicol 2008; 4(1): 77–91PubMedCrossRefGoogle Scholar
Mercadante S, Radbruch L, Caraceni A, et al. Episodic (breakthrough) pain. Consensus conference of an expert working group of the European Association for Palliative Care. Cancer 2002; 94(3): 832–9PubMedCrossRefGoogle Scholar
World Health Organization. WHO’s pain ladder [online]. Available from URL: http://www.who.int/cancer/palliative/painladder/en/ [Accessed 2009 Apr 1]Google Scholar