1,977
Views
131
CrossRef citations to date
0
Altmetric
Original Article

A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial

, , , , , , & show all
Pages 2805-2815 | Accepted 15 Sep 2009, Published online: 30 Sep 2009
 

Abstract

Objective:

The efficacy of intranasal fentanyl spray (INFS) was compared with that of oral transmucosal fentanyl citrate (OTFC) for the relief of cancer-related breakthrough pain (BTP) in an open-label, crossover trial.

Methods:

Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries (Austria, France, Germany, Italy, Poland, Spain and the United Kingdom); of the 196 patients enrolled, 139 were randomised to receive INFS followed by OTFC, or vice versa. Patients were titrated to an effective dose of one agent (50, 100 or 200 µg INFS; 200, 400, 600, 800, 1200 or 1600 µg OTFC) to treat six BTP episodes, then titration and treatment were repeated with the other agent. The primary outcome was patient-recorded time to onset of ‘meaningful’ pain relief. Secondary outcomes included pain intensity difference (PID) at 10 and 30 minutes (PID10, PID30), sum of PID at 15 and 60 minutes (SPID0–15, SPID0–60), ease of administration, treatment preference and relationship between background opioid dose and effective INFS dose. Additional outcome measures included proportions of episodes with ≥33% and ≥50% pain intensity (PI) reduction, and PID at additional time points.

Clinical trial registration number:

NCT00496392.

Results:

Among the intention-to-treat population (n = 139), median time to onset of ‘meaningful’ pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to ‘meaningful’ pain-relief onset with INFS (p < 0.001). PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing. Significantly more INFS-treated breakthrough pain episodes achieved clinically important pain relief (≥33% and ≥50% PI reduction) up to 30 minutes post-dosing. The proportions of episodes treated with INFS and OTFC achieving a PI reduction of ≥33% at 5 minutes were 25.3% versus 6.8% (p < 0.001), and at 10 minutes were 51.0% versus 23.6% (p < 0.001), respectively; the proportions of episodes treated with INFS and OTFC achieving a ≥50% PI reduction at 5 minutes were 12.8% versus 2.1% (p < 0.001), and at 10 minutes were 36.9% versus 9.7% (p < 0.001), respectively. Higher SPID0–15 and SPID0–60 scores were achieved with INFS (p < 0.001). More patients preferred INFS than OTFC (p < 0.001) and more patients found it very easy/easy to use. Both treatments were well tolerated. In the safety population (n = 139), 56.8% (n = 79) of patients experienced ≥1 AE during the trial. The only AE that occurred in ≥5% of patients in either treatment group was nausea. Among those patients who experienced serious AEs (13.7%, n = 19), none were considered to be related to either study medication. There was a weak correlation between effective INFS doses and background opioid doses.

Conclusion:

In this open-label, randomised, crossover trial, significantly more patients attained faster ‘meaningful’ pain relief with INFS than OTFC, and more patients preferred INFS to OTFC.

Transparency

Declaration of funding

This study was funded by Nycomed, Denmark. Nycomed was responsible for both the design and the conduct of the study. Nycomed funded the statistical analysis and medical writing/editing assistance for this manuscript. Relevant parties at Nycomed were allowed the opportunity to comment on the manuscript.

Declaration of financial/other relationships

S.M. has disclosed receiving grant/research funding from Nycomed, Cephalon, Grünenthal, and Mundipharma and acting as a consultant/advisor for Nycomed, Cephalon, Grünenthal, Janssen, GW Pharmaceuticals, Mundipharma and Novartis. L.R. has disclosed acting as a consultant/advisor on Nycomed's German and International Advisory Boards. A.D. has disclosed receiving grant/research funding from Nycomed, acting as a consultant/advisor for Nycomed and speaking at one of their satellite symposia. P. Poulain has disclosed that he has no relevant financial/other relationships. T.S. has disclosed receiving sponsorship from Nycomed, Archimedes, Haupt, Mundipharma and ProStrakan and acting as a consultant/advisor for Nycomed, Grünenthal, Haupt, Archimedes, Jansen-Cilag and Fresenius-Kabi. P. Perkins has disclosed receiving (on behalf of: Sue Ryder Care Leckhampton Court Hospice) grant/research funding for enrolling patients in the present study. T.C. is an employee of Nycomed. M.A.C. has disclosed that he has no relevant financial/other relationships.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he is a shareholder in and former employee of AstraZeneca and a consultant on regulatory affairs to a medical communications company. Peer Reviewer 2 has disclosed that he is a consultant/advisor to and on the speakers bureau for Cephalon, Cephoam, ProStrakan and Nycomed.

Acknowledgements

This study was sponsored by Nycomed, Denmark. Statistical analysis of data was carried out by the independent Contract Research Organisation, PPD (sponsored by Nycomed). Writing/editorial assistance during article preparation was provided by the independent medical communication companies, Wells Healthcare Communications Ltd and Cambridge Medical Communication Ltd (sponsored by Nycomed).

We thank all investigators from the 44 centres involved in the trial, and all patients who took part in the trial.

Part of the data from this study was previously presented as an oral presentation at the 11th Congress of the European Association for Palliative Care, 7–10 May 2009, Vienna, Austria, and presented as posters at the 6th Congress of the European Federation of IASP Chapters, 9–12 September 2009, Lisbon, Portugal.

Notes

*Actiq is a registered trade name of Cephalon, USA.

Instanyl is a registered trade name of Nycomed, Denmark.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.