Rauck, R.L., Tark, M., Reyes, E., Hayes, T.G., Bartkowiak, A.J., Hassman, D., . . . Howell, J. (2009). Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Current Medical Research and Opinion, 25, 2877–2885.

To evaluate the effect of sublingual fentanyl on breakthrough cancer pain in opioid-tolerant patients; to assess how well patients tolerate sublingual fentanyl

The study included an open-label titration phase, a two-week double-blind efficacy phase, and a long-term open-label safety phase of up to 12 months duration. Sublingual orally disintegrating tablet (ODT) fentanyl was given at 100 mcg and titrated in the open-label phase to a maximum dose of 800 mcg until patients identified a single effective and tolerable dose. In the double-blind phase, patients received seven doses of the study drug and three doses of placebo. The study drug and placebo were identical in appearance. Patients took doses in a randomly assigned sequence. Rescue medication could be administered if needed after two hours. Patients were followed on a daily basis by telephone to monitor use of the study and rescue medications and the incidence of adverse events during the titration phase. Thereafter, investigators monitored patients in person on a monthly basis and at two weeks after monthly by-telephone evaluations. Patients maintained an electronic daily diary. Pain intensity  and pain relief were recorded immediately prior to treatment and at 10, 15, 30, and 60 minutes after use.

• The sample was composed of 66 patients in the double-blind phase and 72 in the long-term phase.
• Mean patient age was 55 years (SD = 11.5 years). Age range was 21–80 years.
• Of all patients, 45.8% were male and 54.2% were female.
• Authors did not report specific diagnoses.
• Of all patients, 84% were Caucasian.

• Multisite
• Outpatient

• Phases of care: end of life, palliative care
• Clinical applications: late effects and survivorship

Randomized placebo-controlled phase III trial

• Eleven-point verbal rating scale, to measure pain severity
• Five-point verbal scale, to measure pain relief
• Patient Global Evaluation of Medication
• Evaluation of adverse events by clinicians

Overall, patients received the study drug for an average of 51 days. Median dose of ODT fentanyl was 600 mcg. A median of three doses were taken per day. The most common treatment-related complications were nausea (12.2%), vomiting (5.3%), and somnolence (4.6%). One patient developed stomatitis, which may have been related to the study drug. Sublingual ODT fentanyl was significantly more effective (p < 0.006) than placebo at all time points and was most effective at 60 minutes (p = 0.0004). Pain relief was significantly better with ODT fentanyl than with placebo (p = 0.0007) at 15 minutes after use and at 30 and 60 minutes.

Sublingual ODT fentanyl was effective in the management of breakthrough pain, and patients tolerated the medication well.

• The study had a small sample, with fewer than 100 patients.
• Authors did not discuss the use of rescue medications.
• Authors provided no information about baseline pain levels. Duration or diagnosis was provided to determine generalizability of findings.  No information is provided regarding background pain management or total opiod doses. The follow-up period was relatively short, and a large number of cases were lost to follow-up.

In this study ODT fentanyl was effective in treating breakthrough pain; therefore, ODT fentanyl may be an appropriate means to manage this problem. The study reported one case of stomatitis, which may have been related to this drug. Nurses should be aware of the potential of stomatitis occurring with a patient's use of ODT fentanyl. The follow-up period in the present study was relatively short. Longer use of ODT fentanyl may pose greater risk of stomatitis.