Simon, S.T., Kloke, M., Alt-Epping, B., Gartner, J., Hellmich, M., Hein, R., . . . Voltz, R. (2016). EffenDys-fentanyl buccal tablet for the relief of episodic breathlessness in patients with advanced cancer: A multicenter, open-label, randomized, morphine-controlled, crossover, phase II trial. Journal of Pain and Symptom Management, 52, 617–625.

To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl (FBT) in comparison to immediate-release morphine (IRM) for the relief of episodic breathlessness.

Fentanyl buccal tablets 100 mcg and 2% immediate release morphine are titrated to 1/6th dosing based on their daily oral morphine equivalent (DOME) to start and increase up to 400 mcg fentanyl or 1/6th + 100% of DOME. Patients were to keep a diary of when dyspnea episode started and when medication taken, with various times to record effectiveness and oxygen saturation over one hour. Patients had twice-a-day safety checks by researchers. Actual doses used were 100-200 mcg of fentanyl and 6-36 mg morphine. Patients crossed over after five days (of a 10-day study).

• N = 6 patients completed the study
• AGE: Mean = 58 years old
• MALES: 60%
• FEMALES: 40%
• CURRENT TREATMENT: Palliative care
• KEY DISEASE CHARACTERISTICS: Patients with incurable cancer who had at least one month to live and SOB scores greater than 3 of 10.
• OTHER KEY SAMPLE CHARACTERISTICS: Older than age 18 years and opiate tolerant.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Germany

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Elder care, palliative care

This is an open-label, randomized, active-controlled (morphine), crossover, phase II trial with an open label dose titration phase.

Oxygen saturation testing was done, stop watch, and a breathlessness scale of 0-10, with 10 being the worst score. Respiratory rate, Glasgow Coma Scale, and Karnofsky level.

The Breathlessness Index Difference (BID) was calculated.  At 10 minutes, the difference was p = 0.051, with mean time to onset of meaningful breathlessness relief was for FBT 12.7 minutes (plus or minus 10 minutes), and, for IRM, 23.6 minutes (plus or minus 15.1 minutes), with a mean difference of 10.9 minutes (95% CI [-24.5, 2.7], p = 0.094) in favor for FBT (FBT-IRM). Time of onset between morphine and fentanyl was a mean difference of 8.4 (95% CI [-18.8, 2.1], p = 0.085), which was not statistically significant.

Fentanyl was found to work quicker then MS, without any difference in side effects or satisfaction with the medications.

• Small sample (< 30)

For many patients, once SOB has started, time to relief can be an important factor in keeping the anxiety factor down. For some, the price of fentanyl outweighs the benefit against morphine as both have tolerated side effects for opiate-tolerant patients.