Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase 4 ‘real life’ trial on the variability of response to opioids
Mené en Italie auprès de 520 patients atteints de cancer, cet essai multicentrique de phase IV compare l'efficacité, dans la durée et en fonction de la réponse individuelle du patient, de quatre opioïdes forts pour traiter la douleur liée au cancer
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 were recorded. The primary efficacy endpoint was the proportion of non-responders, meaning patients with worse or unchanged average pain intensity between the first and last visit, measured on a 0 to 10 numerical rating scale. (NCT01809106) Results : Forty-four centers participated in the trial and recruited 520 patients. Worst and average pain intensity decreased over four weeks with no significant differences between drugs. Non-responders ranged from 11.5% for morphine to 14.4% for buprenorphine. Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% with morphine to 121.2% with transdermal fentanyl. Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% with morphine to 12% with oxycodone, discontinuation of treatment from 27% with morphine to 14.5% with fentanyl. Adverse drug reactions 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 non or poor responders.