Long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet for the treatment of breakthrough cancer pain

Background and objectives: Breakthrough cancer pain (BTcP) is a transient exacerbation of cancer pain in patients with otherwise stable, persistent background pain. This study evaluated the long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet (sublingual fentanyl ODT), for the treatment of BTcP in opioid-tolerant patients with cancer. Research design and methods: This was a non-randomized, open-label, multi-center, Phase III study conducted in opioid-tolerant patients (aged >= 17 years) with BTcP. The study comprised a 2-week titration phase, followed by a maintenance phase of up to 12 months. Patients self-administered sublingual fentanyl ODT for episodes of BTcP. Effectiveness was assessed using patients' global evaluation of medication (PGEM), the brief pain inventory (BPI) and the depression, anxiety and positive outlook scale (DAPOS). Adverse events were recorded throughout. Clinical trial registration: NCT00263575 (http://www.clinicaltrials.gov/). Results: Of 139 recruited patients, 69% identified an effective dose of sublingual fentanyl ODT (a dosage that successfully treated all episodes of BTcP over two consecutive days) and entered the maintenance phase, during which they were treated for a median of 149.0 days (mean dose 507.5 mu g). The study recorded a significant increase in reported satisfaction with pain medication at the 6-month and end-of-study visits, compared to screening (p <= 0.01). Evaluation of quality of life using BPI and DAPOS identified no deterioration in scores and significant improvements in certain parameters (p < 0.05). Sublingual fentanyl ODT was well tolerated, with no study drug-related deaths, and 49 patients (35.3%) experiencing >= 1 study drug-related adverse event. The most common of these included nausea (8.6%), constipation (5.8%) and somnolence (5.8%). There was no evidence of sublingual mucosal irritation due to the study medication. The pattern of adverse events was similar to that previously observed with transmucosal fentanyl. Conclusions: Sublingual fentanyl ODT was effective and well tolerated for the long-term treatment of BTcP in opioid-tolerant cancer patients. There was an increase in satisfaction with pain medication during the study, and sublingual fentanyl ODT showed an acceptable safety profile over 12 months of treatment.