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

Abstract

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 µg). 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.

Key words::

• Breakthrough pain
• Cancer
• Effectiveness
• Fentanyl
• Safety
• Sublingual administration
• Transmucosal

Transparency

Declaration of funding

This study was sponsored by ProStrakan Group Ltd. Preparation and publication of this article was supported by ProStrakan.

Declaration of financial/other relationships

S.N. has disclosed that he has acted as a principal investigator and speaker/consultant for Endo Pharmaceuticals. M.W. has disclosed that he has received research support from Endo Pharmaceuticals and Archimedes. S.D. has disclosed that he has acted as a consultant for ProStrakan. R.D. and J.H. have disclosed that they are employees of ProStrakan. D.H. has disclosed that he has no relevant financial relationships.

Acknowledgments

Assistance with writing and preparation of this article was provided by Acumen Healthcare Communications Ltd, supported by ProStrakan. The authors also thank Loray Blair-Britt, Stephen Cohen, Rohit Kapoor and Kirk Lund for helping to conduct this study.

Data in this paper were previously presented as posters at: 20th Annual Clinical Meeting of the American Academy of Pain Management, 2009: Nalamachu S, Howell J, Derrick R. Long-term safety and tolerability of sublingual fentanyl. Abstract 36; and 5th World Congress of the World Institute of Pain, 2009: Rauck R, Derrick R, Howell J. Efficacy and tolerability of sublingual fentanyl in opioid-tolerant cancer patients with breakthrough pain: interim findings from two long-term, Phase III multi-centre studies. Pain Pract 2009;9(s1):93–168.

Notes

*Abstral is a registered trademark of ProStakan, Galashiels, UK.

*Vicodin is a registered trademark of Abbott Laboratories, North Chicago, IL, USA.

*Actiq is a registered trademark of Cephalon Inc., Frazer, PA, USA.

†Effentora and Fentora are registered trademarks of Cephalon Inc., Frazer, PA, USA.