O Corli1, I Floriani2, A Roberto3, M Montanari3, F Galli2, M T Greco4, A Caraceni5, S Kaasa6, T A Dragani7, G Azzarello8, M Luzzani9, L Cavanna10, E Bandieri11, T Gamucci12, G Lipari13, R Di Gregorio14, D Valenti15, C Reale16, L Pavesi17, V Iorno18, C Crispino19, M Pacchioni20, G Apolone21. 1. Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative oscar.corli@marionegri.it. 2. Department of Oncology, Laboratorio di Ricerca Clinica, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan. 3. Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative. 4. Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative Department of Statistics, Università di Milano, Milan. 5. Palliative Care Complex Structure, Terapia del dolore e Riabilitazione, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 6. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Norway. 7. S.S.D. Epidemiology, Genetics and Pharmacogenomics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. 8. Department of Hematology and Oncology, Ospedale di U.O.C. di Oncologia Mirano-ASL 13 Regione Veneto, Mirano. 9. Department of Orthogeriatrics, S.S.D. Cure Palliative, riabilitazione e stabilizzazione E.O. Ospedali Galliera, Genova. 10. Oncology Unit, Ospedale di Piacenza, Piacenza. 11. Unit of Supportive and Simultaneous Care, Medical Oncology Division USL, Modena. 12. UOC Medical Oncology, Ospedale SS Trinità, Sora. 13. Palliative Care, P.O. di Salemi-ASP 9, Trapani. 14. U.O.S Obstetric Anasthesia and Pain Therapy, Opedale Sacro Cuore di Gesù - Fatebenefratelli, Benevento. 15. Palliative Care Unit, Azienda Ospedaliera Valtellina e Valchiavenna, Morbegno. 16. Department of Cardiovascular Sciences, Respiratory, Nephrological, Anaesthetics and Geriatrics, Policlinico Universitario Umberto I, Rome. 17. Unit of Oncology, RCCS-Fondazione Salvatore Maugeri, Pavia. 18. Centre for Pain Medicine M. TIENGO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan. 19. UOSD Treatment of Lung Cancer Complications, AO Dei Colli Monaldi Cotugno CTO Ospedale Monaldi, Napoli. 20. Department of Oncology, Ospedale San Raffaele IRCCS, Milan. 21. Scientific Direction, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
BACKGROUND: Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. PATIENT AND METHODS: In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106). RESULTS:Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine. CONCLUSION: The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders. CLINICAL TRIAL REGISTRATION: NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).
RCT Entities:
BACKGROUND: Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. PATIENT AND METHODS: In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106). RESULTS: Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine. CONCLUSION: The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders. CLINICAL TRIAL REGISTRATION: NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).
Authors: Francesco Amato; Silvia Ceniti; Sergio Mameli; Giovanni M Pisanu; Renato Vellucci; Vincenzo Palmieri; Leonardo Consoletti; Dorotea Magaldi; Paolo Notaro; Claudio Marcassa Journal: Support Care Cancer Date: 2017-05-03 Impact factor: 3.603
Authors: Mia Schmidt-Hansen; Michael I Bennett; Stephanie Arnold; Nathan Bromham; Jennifer S Hilgart Journal: Cochrane Database Syst Rev Date: 2017-08-22