Fallon, M., Reale, C., Davies, A., Lux, A.E., Kumar, K., Stachowiak, A., & Galvez, R. (2011). Efficacy and safety of fentanyl pectin nasal spray compared with immediate-release morphine sulfate tablets in the treatment of breakthrough cancer pain: A multicenter, randomized, controlled, double-blind, double-dummy multiple-crossover study. Journal of Supportive Oncology, 9(6), 224–231.

To compare the efficacy and tolerability of fentanyl-pectin spray (FPNS) with that of immediate-release morphine sulfate (IRMS) in the treatment of breakthrough cancer pain (BTCP)

Patients in the study were experiencing 1–4 episodes of BTCP per day while taking at least 60 mg/day of oral morphine or equivalent for BTCP. Patients completing the titration phase continued to the double-blind, double-dummy phase: 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (5 episodes) or IRMS and nasal spray placebo (5 episodes). The primary end point was pain intensity (PI) difference from baseline at 15 minutes. Secondary end points were onset PI decrease (≥ 1 point) and time to clinically meaningful pain relief. Safety and tolerability were evaluated by means of adverse events (AEs) and nasal assessments. By-patient and by-episode analysis were completed. Duration of follow-up was a maximum of 14 days in the open-label period.

• The sample was composed of 110 patients.   
• Mean patient age at baseline was 55.9 years (SD = 12.3 years). Of all patients, 65.1% were 60 years old or younger.
• Of all patients, 53.8% were male and 46.2% were female.
• All patients received fixed-schedule opioid regimens consisting of a total dose equal to or greater than 60 mg/day oral morphine for BTCP. All patients had 1-4 episodes per day of BTCP.
• Exclusion criteria barred participation of patients
  • With uncontrolled or rapidly escalating background pain.
  • Who were medically unstable.
  • Who had breakthrough pain unrelated to cancer.
  • With a past inability to tolerate fentanyl or other opioids.
  • Who anticipated receiving therapy with any pain-affecting treatment (i.e., radiotherapy, chemotherapy) during the study or who had received treatment with another investigational drug within 30 days.
  • With any disorder or using any medication likely to adversely affect normal functioning of the nasal mucosa.

• Multicenter (35 oncology centers)
• Europe and India
   

• Phase of care: active treatment
• Clinical application: palliative care

Randomized, controlled, double-blind, double-dummy, multiple crossover trial

• 11-point numeric scale (0 = no pain, 10 = worst possible pain), to measure pain intensity.
• Nasal assessments performed by the study physician.
• Four-point scale (0 = absent, 3 = severe) of subjective nasal assessment by the patient, who completed a 10-item questionnaire before the first use of the study drug, one hour after each dose of the study medication, and at the final study visit. Items rated included stuffy/blocked nose, runny nose, itching/sneezing, crusting/dryness, burning/discomfort, nosebleed, cough, postnasal drip, sore throat, and taste disturbance.
   

• Analysis of pain intensity difference pre- and post-treatment showed that FPNS provided a greater reduction in pain intensity than did IRMS, with mean ± SE 3.02 ± 0.21 for FPNS doses and 2.69 ± 0.18 for IRMS (p < 0.05). Statistical superiority of FPNS compared with IRMS, on patient-averaged PID scores, continued at each point 15–60 minutes (p < 0.05).
• After treatment, from 10 minutes onward, mean PI scores were lower for FPNS-treated episodes than for IRMS-treated episodes.
• More treatment-emergent AEs occurred after FPNS than after IRMS treatment. A higher percentage of treatment-emergent AEs occurred after 400 mcg and 800 mcg doses of FPNS. Treatment-emergent AEs were mainly mild to moderate in severity and included vomiting, somnolence, dehydration, and nausea. Of all patients, 4.7% of patients withdrew from titration due to AEs.
   

The pain intensity difference associated with FPNS was greater than that associated with IRMS. The difference between the two measures of pain intensity was statistically significant (p < 0.05).

• The study was of short duration, only 14 days. This period is not long enough to evaluate potential long-term effects on the nasal mucosa.
• The study design did not include titration to an effective dose of IRMS.

For patients receiving around-the-clock opioid treatment for chronic cancer-related breakthrough pain, FPNS appears to be effective, safe, and well tolerated. The early reduction of pain that FPNS provided either matched or exceeded that provided by IRMS. Compared to IRMS, FPNS provided more complete pain relief. The effects of long-term use of FPNS have not been evaluated; nurses must be aware that long-term effects of FPNS on the nasal mucosa are unknown.