title: Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).
authors.affiliation: Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative. Electronic address: oscar.corli@marionegri.it.
authors.forename: O
authors.initials: O
authors.lastname: Corli
authors.affiliation: Department of Oncology, Laboratorio di Ricerca Clinica, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan.
authors.forename: I
authors.initials: I
authors.lastname: Floriani
authors.affiliation: Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative.
authors.forename: A
authors.initials: A
authors.lastname: Roberto
authors.affiliation: Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative.
authors.forename: M
authors.initials: M
authors.lastname: Montanari
authors.affiliation: Department of Oncology, Laboratorio di Ricerca Clinica, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan.
authors.forename: F
authors.initials: F
authors.lastname: Galli
authors.affiliation: Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative; Department of Statistics, Università di Milano, Milan.
authors.forename: M T
authors.initials: MT
authors.lastname: Greco
authors.affiliation: Palliative Care Complex Structure, Terapia del dolore e Riabilitazione, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Caraceni
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Kaasa
authors.affiliation: S.S.D. Epidemiology, Genetics and Pharmacogenomics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: T A
authors.initials: TA
authors.lastname: Dragani
authors.affiliation: Department of Hematology and Oncology, Ospedale di U.O.C. di Oncologia Mirano-ASL 13 Regione Veneto, Mirano.
authors.forename: G
authors.initials: G
authors.lastname: Azzarello
authors.affiliation: Department of Orthogeriatrics, S.S.D. Cure Palliative, riabilitazione e stabilizzazione E.O. Ospedali Galliera, Genova.
authors.forename: M
authors.initials: M
authors.lastname: Luzzani
authors.affiliation: Oncology Unit, Ospedale di Piacenza, Piacenza.
authors.forename: L
authors.initials: L
authors.lastname: Cavanna
authors.affiliation: Unit of Supportive and Simultaneous Care, Medical Oncology Division USL, Modena.
authors.forename: E
authors.initials: E
authors.lastname: Bandieri
authors.affiliation: UOC Medical Oncology, Ospedale SS Trinità, Sora.
authors.forename: T
authors.initials: T
authors.lastname: Gamucci
authors.affiliation: Palliative Care, P.O. di Salemi-ASP 9, Trapani.
authors.forename: G
authors.initials: G
authors.lastname: Lipari
authors.affiliation: U.O.S Obstetric Anasthesia and Pain Therapy, Opedale Sacro Cuore di Gesù - Fatebenefratelli, Benevento.
authors.forename: R
authors.initials: R
authors.lastname: Di Gregorio
authors.affiliation: Palliative Care Unit, Azienda Ospedaliera Valtellina e Valchiavenna, Morbegno.
authors.forename: D
authors.initials: D
authors.lastname: Valenti
authors.affiliation: Department of Cardiovascular Sciences, Respiratory, Nephrological, Anaesthetics and Geriatrics, Policlinico Universitario Umberto I, Rome.
authors.forename: C
authors.initials: C
authors.lastname: Reale
authors.affiliation: Unit of Oncology, RCCS-Fondazione Salvatore Maugeri, Pavia.
authors.forename: L
authors.initials: L
authors.lastname: Pavesi
authors.affiliation: Centre for Pain Medicine M. TIENGO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan.
authors.forename: V
authors.initials: V
authors.lastname: Iorno
authors.affiliation: UOSD Treatment of Lung Cancer Complications, AO Dei Colli Monaldi Cotugno CTO Ospedale Monaldi, Napoli.
authors.forename: C
authors.initials: C
authors.lastname: Crispino
authors.affiliation: Department of Oncology, Ospedale San Raffaele IRCCS, Milan.
authors.forename: M
authors.initials: M
authors.lastname: Pacchioni
authors.affiliation: Scientific Direction, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Apolone
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D000072716:Cancer Pain / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D010098:Oxycodone; D005283:Fentanyl
keywords: changes of therapy; neurotoxic effects; opioids in cancer pain; variability of response