Nalamachu, S., Hassman, D., Wallace, M.S., Dumble, S., Derrick, R., & Howell, J. (2011). Long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet for the treatment of breakthrough cancer pain. Current Medical Research and Opinion, 27(3), 519–530.

To evaluate the long-term effectiveness of sublingual fentanyl orally disintegrating tablets (ODTs) for the treatment of breakthrough cancer pain in opioid-tolerant patients

The study comprised a two-week titration phase to establish an effective dose of sublingual fentanyl ODT. If an effective dose was achieved, the patient entered a maintenance phase that lasted up to 12 months. During the maintenance phase, patients self-administered sublingual fentanyl ODTs at the dose identified in the titration phase. Effectiveness of pain regimen was assessed at screening and at each monthly visit.

• The sample was composed of 139 patients.
• Mean patient age was 57 years (SD = 11.6 years). The age range was 28–85 years.
• Of all patients, 54.7% were female and 45.3% were male.
• All patients were experiencing cancer-related background pain, with 1–4 episodes of breakthrough cancer pain daily. All patients were on a fixed-schedule oral opioid regimen equivalent to 60–1000 mg oral morphine per day or transdermal fentanyl therapy equivalent to 50–300 mcg/hour.
• All patients were Eastern Cooperative Oncology Group performance status 0–2.
• Of all patients, 116 (83.5%) were white.

Multisite (44 sites in the United States)

Nonrandomized, open-label, phase III study

• Patient Global Evaluation of Medication scale, a one-question assessment that asks the patient \"How satisfied are you overall with your current medication for pain?\"
• Brief Pain Inventory (BPI), to measure pain and physical functioning
• Depression, Anxiety, and Positive Outlook Scale (DAPOS)

• Sixty-two patients received sublingual fentanyl ODTs for at least 3 months; 19 were treated for 12 months. Mean duration of the maintenance phase was 149 days.
• Of 92 patients, 77% (71 patients) were very satisfied or satisfied with their pain medication at the end of the study.
• Scores obtained at screening and at the six-month visit showed a significant (p = 0.001) increase in reported satisfaction.
• The BPI scores of 85 patients showed that current pain was significantly (p ≤ 0.01) lower at  six months than at screening. Compared to pain relief at screening, pain relief had improved significantly at the six-month and end-of- study visits (p < 0.05).
• Depression scores showed a statistically significant (p = 0.011) improvement at six months.
• The median stable dose of sublingual fentanyl ODT identified during the titration phase was 400 mcg (range, 100–800 mcg; mean, 475.0 mcg).
• The most common adverse effects related to sublingual fentanyl ODTs were nausea (8.6%, or 12 of 139 patients), constipation (5.8%, or 8 of 139 patients), and somnolence (5.8%, or 8 of 139 patients).

Sublingual fentanyl ODT may provide effective analgesia while maintaining quality of life during long-term treatment of breakthrough cancer pain.

• The study had a small sample size, with fewer than 30 patients.
• The single-arm design of this study was a limitation as was the large number of withdrawals. Of 139 patients, 120 withdrew: 37 for adverse events, 32 as the result of sponsor or investigator decisions, 18 following withdrawal of consent, 13 as the result of protocol violations, 10 for lack of efficacy, and 10 for other reasons unspecified. Forty-three withdrew during the required titration phase, decreasing sample size from 139 to 96.
• Analysis was done on the 139 patients who entered the titration phase and the 96 who completed the titration phase, not the 19 who completed the maintenance phase. This may have had an impact on the outcomes at patient-assessed endpoints and on the generalizability of the study.
• The study did not follow patients through the most advanced stages of their illness.

Study of a larger and more racially diverse patient population, over a longer period of time, is required. Additional research in a palliative care setting may be warranted.