1. Fentanyl Pectin Nasal Spray: Successful Dose Titration in a Broad Range of Patients with Breakthrough Cancer Pain
Luis Torres,1 Carlo Reale,2 Eberhard A. Lux,3 Louise Lynch,4 Julia Revnic,5 Andrew Davies6
1Servicio de Anestesia/Puerta del Mar, Cadiz, Spain
2Sapienza University of Rome, Rome, Italy
3St. Marien-Hospital, Lünen, Germany
4St. James's Institute of Oncology, Leeds, United Kingdom
5Hôpital de l'hotel Dieu, Paris, France
6The Royal Marsden NHS Foundation Trust, Surrey, United Kingdom

2. Study Objective and Proper Titration of FPNS
Study objective: To analyse open-label, dose-titration outcomes in the FPNS phase III clinical trial programme in cancer patients with BTCP
Background pain: ATC medications should be adjusted so that no more than four episodes of BTCP are experienced each day
FPNS Dosing:
FPNS is available in two strengths: 100 and 400 μg
One spray of 100 μg in each nostril = 200 μg
One spray of 400 μg in each nostril = 800 μg
Initial Dose: One 100-μg spray
Patients must wait at least 4 hours before treating another episode of BTCP with FPNS
The dose that effectively treats two consecutive episodes of BTCP without unacceptable AEs is considered an effective dose
Maintenance: Established effective dose up to a maximum of four doses per day
As this analysis is on the dose titration outcomes of the FPNS phase III clinical trial programme, let’s briefly review the FPNS titration process.
FPNS is available in two strengths (100 μg and 400 μg). These two strengths are able to create the 200 μg and 400 μg and 800 μg doses by using one spray in each nostril with the 100 μg and 400 μg FPNS strengths, respectively. The initial dose is one spray of 100 μg. Before using a higher dose the patient must wait at least 4 hours. If the strength is inadequate the patient may titrate-up to the next dose (ie, 2 sprays of 100 μg). This process is repeated until the patient finds a dose that that effectively treats two consecutive episodes of BTCP without unacceptable AEs. The patient should be advised that only 4 doses can be used per day.

3. Fentanyl Pectin Nasal Spray Phase III Clinical Trial Programme: Overview of Patient Characteristics
Safety population* consisted of 500 patients from the three phase III clinical trials
Age: mean ranged from 53.6 y – 55.9 y (range: 18–86 y)
Gender: evenly distributed (male, 52.6%; female, 47.4%)
Race: a broad range of races were included
Nearly 40% were Indian, Hispanic, American Indian, or Pacific Islander
Caucasians made up 53.6% of the population
Weight: mean ranged from 59.8 kg to 78.8 kg (range: 30.0–149.9 kg)
ECOG score: most were ECOG score 1 or 2 (n = 438/500; 87.6%)
BTCP severity
All considered their pain to be moderate (n = 98/500 [19.6%]) or severe (n = 399/500 [79.8%])
According to the patients this pain occurred between 1 and 25 times a day (means ranged between 2.3 to 3.4)
This analysis is based on the safety population from the three phase III FPNS clinical trials. The safety population consisted of those patients that received at least one dose of FPNS. The majority of the patients in this population were in their mid-fifties, were male, and were Caucasian. Weight varied widely, but most were between 60 kg and 80 kg. The vast majority of patients were ECOG score 1 or 2 (nearly 90%) and all patients considered their BTCP pain moderate or severe. Surprisingly, this pain was reported to occur as many as 25 times in some, but the average of 2.3 to 3.4 is consistent with the published literature.
ECOG, Eastern Cooperative Oncology Group.
*Patients that received at least one dose of FPNS.

4. Phase III Clinical Trial Programme: Patient Distribution by Effective Titrated Dose of FPNS
As we can see on this slide the successfully titrated dose of FPNS was well distributed, and was not dramatically slanted to one particular dose.

5. Total Treated (Safety Population)
Phase III Clinical Trial Programme: Reasons for Withdrawal from Open Dose-Titration Phase
Reasons for Withdrawal from Open Dose-Titration Phase
Total Treated (Safety Population)
Adverse event
14 (2.8)
Lack of efficacy
27 (5.4)
Did not continue to meet study criteria
17 (3.4)
Inability to evaluate/record subject assessment data
1 (0.2)
Death (not study drug related)
5 (1.0)
Inability to explain return of less medication than predicted
2 (0.4)
Lost to follow-up
Protocol violation
Withdrawal of consent
Other
13 (2.6)
Overall, there was only a small number of withdrawals from the open-label dose titration phase. Of those that could have been as a result of FPNS treatment (ie, adverse event and lack of efficacy) there were only 41 instances (8.2%).
*Newly enrolled patients.

6. No Correlation Between Effective Titrated Dose of FPNS and Age90 80 70 60 50
Age, y 40 30
This evaluation, which looked at the age of the patients according to their effective titrated dose of FPNS, clearly demonstrates that there was no significant difference between the doses. 20 10
100 μg
200 μg
400 μg
800 μg
Titrated Dose of FPNS

7. No Correlation Between Effective Titrated Dose of FPNS and Weight or Gender
Weight by Titrated Dose/Gender = Males
Weight by Titrated Dose/Gender = Females
160
160
140
140
120
120
100
100
Weight, Kg
Weight, Kg 80 80
This evaluation, which looked at the weight of the patients by gender according to their effective titrated dose of FPNS, clearly demonstrates that there was no significant difference between the doses as well. 60 60 40 40 20 20
100 μg
200 μg
400 μg
800 μg
100 μg
200 μg
400 μg
800 μg
Titrated Dose of FPNS
Titrated Dose of FPNS

8. Conclusions
FPNS is easily titrated to an effective dose and can be used across a broad range of opioid-tolerant cancer patients, with only 8.0% unable to titrate for FPNS-related reasons
Rate of success was consistent across the three multinational, multicentre studies at sites in 13 countries and four continents
Dose titration did not vary by country, age, or weight