Rauck, R., North, J., Gever, L.N., Tagarro, I., & Finn, A.L. (2010). Fentanyl buccal soluble film (FBSF) for breakthrough pain in patients with cancer: A randomized, double-blind, placebo-controlled study. Annals of Oncology: Official Journal of the European Society for Medical Oncology/ESMO, 21(6), 1308–1314.

To evaluate the efficacy of fentanyl buccal soluble film (FBSF), at doses of 200–1200 mcg, in the management of breakthrough pain (BTP) in patients with cancer who are receiving ongoing opioid therapy

In phase 1, patients were screened, for up to one week, to assess tolerance of FBSF. In phrase 2, the titration phase, patients started with 200 mcg dose that was increased in a stepwise fashion (200, 400, 600, 800, 1200 mcg) until the patient experienced pain relief. Patients were discontinued from the study if a satisfactory dose could not be determined. If a satisfactory dose was achieved for two BTP episodes, patients proceeded to the double-blind phase. The double-blind phase lasted up to two weeks. Each patient received nine doses of FBSF (six of study medication and three of placebo). A computer determined the order of administration. Patients were allowed to use usual rescue medication if they did not receive adequate pain relief in 30 minutes. Study medication was allowed every four hours.

• The safety population consisted of 151 patients; 82 patients were in the efficacy population (double-blind phase).
• The study comprised 394 FBSF-treated episodes and 197 placebo-treated episodes.
• In the safety population, mean patient age was 57.1 years. In the efficacy population, mean patient age was 56.8 years.
• In the safety population, 56% were female and 44% were male. In the efficacy population, 55% were female and 45% were male.
• In regard to diagnosis, the conditions that follow were represented in the sample at the cited percentages: breast cancer, 23%; lung cancer, 17%; colorectal cancer, 11%; gastroesophageal cancer, 7%; pancreatic cancer, 6%; head and neck cancer, 5%; nociceptive pain, 50%; neuropathic pain, 32.5%.

• Multisite
• Outpatient
• Thirty centers in the United States

Randomized placebo-controlled, double-blind, multiple-crossover study

• A 0–10 scale (0 = no pain, 10 = worst pain), to measure pain intensity (PI)
• A 0–4 scale (0 = no relief, 4 = complete relief), to measure pain relief
• A measure of pain intensity difference (PID): baseline pain intensity – pain intensity at assessment point
• The sum of pain intensity difference (SPID): sum of PI differences 30 minutes postdose
• A five-point scale of global satisfaction (poor–excellent), with measures taken at the time of rescue-drug administration and 60 minutes postadministration of study drug
• LSM (least-squares mean) ± SEM (standard error mean) = outcome

• For both groups, PI baseline mean was 6.9 and median was 7.0.
• LSM was greater for FBSF-treated episodes than for placebo-treated episodes (47.9 ± 3.9 versus 38.1 ± 4.3) (p = 0.004).
• Results revealed statistically significant separation from placebo at 15 minutes postdose (p < 0.05) through 60 minutes postdose [the last time point assessed (p < 0.001)].
• PID values for FBSF-treated episodes were greater at all time points and significant at 30 minutes (p < 0.01) through last assessment (p < 0.01).
• The percentage of episodes with 33% or 50% decrease in pain was significant compared to the percentage of those episodes related to placebo.
• Satisfaction was greater with FBSF compared to placebo (mean 2.0 versus 1.5, respectively; p < 0.001).
• Mean (± SEM) number of episodes when rescue medication was used was significantly lower after treatment with FBSF than with placebo (30% ± 3.5% versus 44.6% ± 4.4%, p = 0.002).
• Twenty-three patients, or 15.2%, experienced serious adverse events, but according to investigators no event was related to the study drug. Treatment-related adverse events in the titration phase included the conditions that follow, at the cited percentages of patients affected: nausea, 9%; vomiting, 9.3%; somnolence, 6%; dizziness, 4.6%; headache, 4%. Adverse events in the double-blind phase phase included the conditions that follow, at the cited percentages of patients affected: nausea, 9.9%; vomiting, 9.9%; headache, 1.2%.
• Overall satisfaction was higher for FBSF, although a placebo effect did exist (67.1% for FBSF and 47.1% for placebo).

FBSF was more effective than placebo for the treatment of breakthrough pain in patients with cancer. The treatment was well tolerated.

• The study had a small sample, with fewer than 100 participants.
• Not all patients completed all measures.

FBSF shows favorable and safe results for the treatment of breakthrough pain, but the treatment remains investigational.