title: Comparison of the Tolerability Profile of Controlled-Release Oral Morphine and Oxycodone for Cancer Pain Treatment. An Open-Label Randomized Controlled Trial.
abstract: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Zecca
authors.affiliation: 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.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Brunelli
authors.affiliation: Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bracchi
authors.affiliation: Emergency Medicine Unit, Istituto Clinico Humanitas Rozzano, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biancofiore
authors.affiliation: Oncology Unit Ospedale San Gennaro, Napoli, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: De Sangro
authors.affiliation: Palliative Care and Pain Therapy Unit, CRO Aviano National Cancer Institute, Aviano, Pordenone, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bortolussi
authors.affiliation: Palliative Care Unit, AUSL Della Romagna, Ravenna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Montanari
authors.affiliation: Palliative Care Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Maltoni
authors.affiliation: Medical Oncology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Moro
authors.affiliation: Pain and Palliative Medicine Unit, AAS 2 Bassa Friulana-Isontina, Latisana, Udine, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Colonna
authors.affiliation: Department of Medical sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Finco
authors.affiliation: Hospice e Cure Palliative, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Roy
authors.affiliation: Medical Oncology Unit, A.O. Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Ferrari
authors.affiliation: Oncology Unit, Ospedale di Novara, Novara, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Alabiso
authors.affiliation: Medical Oncology, Ospedale Regionale Treviso, Treviso, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rosti
authors.affiliation: 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.
authors.forename: Stein
authors.initials: S
authors.lastname: Kaasa
authors.affiliation: 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.
authors.forename: Augusto
authors.initials: A
authors.lastname: Caraceni
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D000072716:Cancer Pain / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects; D010147:Pain Measurement; D010166:Palliative Care; D012306:Risk; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009020:Morphine; D010098:Oxycodone
keywords: Morphine; adverse drug reactions; cancer; oxycodone; pain; palliative care