Efficacy of intranasal fentanyl spray versus other opioids for breakthrough pain in cancer

Objective: To compare the efficacy of intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC), fentanyl buccal tablet (FBT) and oral morphine (OM) for the treatment of breakthrough cancer pain (BTCP). Methods: A systematic literature review (Medline, EMBASE, BIOSIS; 1996-2007) identified six randomised controlled trials (RCTs) investigating the effects of INFS, OTFC, FBT and OM for the treatment of BTCP. The endpoint of interest was pain intensity difference (PID, reported on a 0-10 numeric rating scale [NRS]) up to 60 minutes after intake. Results of all trials were analysed simultaneously with a mixed treatment comparison (extended meta-analysis). MTC can be considered a valid method when included studies are comparable regarding effect modifying baseline patient and study characteristics. Results: INFS provided the greatest reduction in pain relative to placebo: PID 1.7 points (95% CrI: 1.4; 1.9) at 15 minutes, 2.0 (1.6; 2.3) at 30 minutes, 2.0 (1.5; 2.4) at 45 minutes and 1.9 (1.5; 2.4) at 60 minutes. PID for OTFC and FBT relative to placebo were 0.4 (0.0; 0.8) and 0.5 (0.3; 0.7) at 15 minutes. Both treatments provided a reduction in pain superior to placebo at other time points. INFS displayed a more than 99% probability of providing the greatest pain reduction out of all interventions compared at 15 minutes after intake. This was maintained for any measured time point before 45 minutes when compared to FBT and for any measured time point before 60 minutes when compared to OTFC. Only from 45 minutes onwards did OM show a greater pain reduction than placebo. Conclusion: Based on currently available evidence, INFS is expected to provide the greatest improvement in the treatment of BTCP. Due to its slow onset to effect OM cannot be considered an efficacious treatment for BTCP.