Objective: The efficacy of intranasal fentanyl spray (INFS) was compared with that of oral transmucosal fentanyl citrate (OTFC) for the relief of cancer-related breakthrough pain (BTP) in an open-label, crossover trial.
Methods: Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries (Austria, France, Germany, Italy, Poland, Spain and the United Kingdom); of the 196 patients enrolled, 139 were randomised to receive INFS followed by OTFC, or vice versa. Patients were titrated to an effective dose of one agent (50, 100 or 200 microg INFS; 200, 400, 600, 800, 1200 or 1600 microg OTFC) to treat six BTP episodes, then titration and treatment were repeated with the other agent. The primary outcome was patient-recorded time to onset of 'meaningful' pain relief. Secondary outcomes included pain intensity difference (PID) at 10 and 30 minutes (PID(10), PID(30)), sum of PID at 15 and 60 minutes (SPID(0-15), SPID(0-60)), ease of administration, treatment preference and relationship between background opioid dose and effective INFS dose. Additional outcome measures included proportions of episodes with > or =33% and > or =50% pain intensity (PI) reduction, and PID at additional time points.
Clinical trial registration number: NCT00496392.
Results: Among the intention-to-treat population (n = 139), median time to onset of 'meaningful' pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to 'meaningful' pain-relief onset with INFS (p < 0.001). PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing. Significantly more INFS-treated breakthrough pain episodes achieved clinically important pain relief (> or =33% and > or =50% PI reduction) up to 30 minutes post-dosing. The proportions of episodes treated with INFS and OTFC achieving a PI reduction of > or =33% at 5 minutes were 25.3% versus 6.8% (p < 0.001), and at 10 minutes were 51.0% versus 23.6% (p < 0.001), respectively; the proportions of episodes treated with INFS and OTFC achieving a > or =50% PI reduction at 5 minutes were 12.8% versus 2.1% (p < 0.001), and at 10 minutes were 36.9% versus 9.7% (p < 0.001), respectively. Higher SPID(0-15) and SPID(0-60) scores were achieved with INFS (p < 0.001). More patients preferred INFS than OTFC (p < 0.001) and more patients found it very easy/easy to use. Both treatments were well tolerated. In the safety population (n = 139), 56.8% (n = 79) of patients experienced > or =1 AE during the trial. The only AE that occurred in > or =5% of patients in either treatment group was nausea. Among those patients who experienced serious AEs (13.7%, n = 19), none were considered to be related to either study medication. There was a weak correlation between effective INFS doses and background opioid doses.
Conclusion: In this open-label, randomised, crossover trial, significantly more patients attained faster 'meaningful' pain relief with INFS than OTFC, and more patients preferred INFS to OTFC.