Ernesto Zecca1, Cinzia Brunelli2, Paola Bracchi1, Giuseppe Biancofiore3, Carlo De Sangro4, Roberto Bortolussi5, Luigi Montanari6, Marco Maltoni7, Cecilia Moro8, Ugo Colonna9, Gabriele Finco10, Maria Teresa Roy11, Vittorio Ferrari12, Oscar Alabiso13, Giovanni Rosti14, Stein Kaasa15, Augusto Caraceni16. 1. Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 2. Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: cinzia.brunelli@istitutotumori.mi.it. 3. Emergency Medicine Unit, Istituto Clinico Humanitas Rozzano, Milano, Italy. 4. Oncology Unit Ospedale San Gennaro, Napoli, Italy. 5. Palliative Care and Pain Therapy Unit, CRO Aviano National Cancer Institute, Aviano, Pordenone, Italy. 6. Palliative Care Unit, AUSL Della Romagna, Ravenna, Italy. 7. Palliative Care Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy. 8. Medical Oncology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy. 9. Pain and Palliative Medicine Unit, AAS 2 Bassa Friulana-Isontina, Latisana, Udine, Italy. 10. Department of Medical sciences "M. Aresu", University of Cagliari, Cagliari, Italy. 11. Hospice e Cure Palliative, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 12. Medical Oncology Unit, A.O. Spedali Civili di Brescia, Brescia, Italy. 13. Oncology Unit, Ospedale di Novara, Novara, Italy. 14. Medical Oncology, Ospedale Regionale Treviso, Treviso, Italy. 15. European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway. 16. Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Abstract
CONTEXT: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations. OBJECTIVES: This study was mainly aimed at comparing the risk of developing adverse events (AEs) with controlled-release oral morphine vs. oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups. METHODS: An open-label multicenter RCT (EudraCT number: 2006-003151-21) was carried out in patients with moderate/severe cancer pain. At baseline, 7 and 14 days, patients scored on 0-10 rating scales (0-10 numerical rating scale) the intensity of pain and of a list of common opioid side effects. The primary end point was the percentage of patients reporting an AE (a worsening ≥ 2 points on any of the listed side effects); tolerability by subgroups and average follow-up pain intensity were compared through regression models. RESULTS:One hundred eighty-seven patients were enrolled (47% of originally planned). Intention to treat (ITT) analysis (N = 185, morphine 94, oxycodone 91) did not show any difference in the risk of developing AEs (risk difference -0.6%, 95% CI -11.0% to 9.9%) nor in analgesia (0-10 numerical rating scale pain intensity difference -0.28, 95% CI -0.83 to 0.27). No evidence of heterogeneity of tolerability across age and renal function patient subgroups emerged. CONCLUSION: This trial failed to show any difference in tolerability and analgesic efficacy of morphine and oxycodone as first-line treatment for moderate/severe cancer pain but results interpretation is difficult due to lack of power, potential bias from open-label design, and concerns about assay sensitivity. These data, however, can significantly contribute to future meta-analyses comparing WHO Step-III opioids and are relevant in designing future randomized studies.
RCT Entities:
CONTEXT: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations. OBJECTIVES: This study was mainly aimed at comparing the risk of developing adverse events (AEs) with controlled-release oral morphine vs. oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups. METHODS: An open-label multicenter RCT (EudraCT number: 2006-003151-21) was carried out in patients with moderate/severe cancer pain. At baseline, 7 and 14 days, patients scored on 0-10 rating scales (0-10 numerical rating scale) the intensity of pain and of a list of common opioid side effects. The primary end point was the percentage of patients reporting an AE (a worsening ≥ 2 points on any of the listed side effects); tolerability by subgroups and average follow-up pain intensity were compared through regression models. RESULTS: One hundred eighty-seven patients were enrolled (47% of originally planned). Intention to treat (ITT) analysis (N = 185, morphine 94, oxycodone 91) did not show any difference in the risk of developing AEs (risk difference -0.6%, 95% CI -11.0% to 9.9%) nor in analgesia (0-10 numerical rating scale pain intensity difference -0.28, 95% CI -0.83 to 0.27). No evidence of heterogeneity of tolerability across age and renal function patient subgroups emerged. CONCLUSION: This trial failed to show any difference in tolerability and analgesic efficacy of morphine and oxycodone as first-line treatment for moderate/severe cancer pain but results interpretation is difficult due to lack of power, potential bias from open-label design, and concerns about assay sensitivity. These data, however, can significantly contribute to future meta-analyses comparing WHO Step-III opioids and are relevant in designing future randomized studies.
Authors: Mia Schmidt-Hansen; Michael I Bennett; Stephanie Arnold; Nathan Bromham; Jennifer S Hilgart; Andrew J Page; Yuan Chi Journal: Cochrane Database Syst Rev Date: 2022-06-09
Authors: Salimah H Meghani; William E Rosa; Jesse Chittams; April Hazard Vallerand; Ting Bao; Jun J Mao Journal: Pain Manag Nurs Date: 2019-09-06 Impact factor: 1.929
Authors: Mia Schmidt-Hansen; Michael I Bennett; Stephanie Arnold; Nathan Bromham; Jennifer S Hilgart Journal: Cochrane Database Syst Rev Date: 2017-08-22