A dose titration study of fentanyl buccal soluble film for breakthrough cancer pain in Taiwan

Abstract

Background: Fentanyl buccal soluble film (FBSF), a new formulation of fentanyl, is developed for the treatment of breakthrough pain (BTP) in opioid-tolerant patients with cancer.Aims: This study aimed to assess the feasible dose range of FBSF required for Taiwanese population. Methods and results:This was an open-label, multicenter, noncomparative study.Cancer patients who were aged 20 years or older and had a stable regimen equivalent to 60 to 1000 mg/day of oral morphine, 20 to 120 mg/day of intravenous morphine, or 25 to 300 μg/h of transdermal fentanyl for at least 1 week were enrolled. The primary endpoint was the feasible dose range of FBSF. Secondary endpoints included difference in pain intensity at 30 minutes (PID30), percentage of episodes requiring rescue medication, and overall satisfaction. Adverse events (AEs) and serious AEs (SAEs) were recorded for safety measurements. The final effective dose in the per-protocol (PP) population (n = 30) ranged from 200 to 800 μg, of which 26 subjects (86.7%) achieved an effective dose range of 200 to 400 μg. Among the 283 BTP episodes recorded in the maintenance period, the mean PID30 was 4.0, and only 13 events (4.6%) required rescue medication. For 63.6% of the BTP episodes, patients rated their satisfaction as good to excellent. Only 5% of AEs were considered drug-related. Conclusions:Individualized dose titration is recommended for BTP management for patients' benefit. Overall, FBSF was effective and well tolerated and was positively correlated with patients' background opioid dose for persistent pain management. KEYWORDSbreakthrough pain, dose titration, feasible dose range, fentanyl buccal soluble film

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control

“…In the first dose titration study of FBSF by Chiou et al [23], FBSF was administrated in a dose titration manner until meaningful pain relief was achieved, and the dose was not allowed to be adjusted during the subsequent 7-day maintenance period even if the disease progressed. However, 4.6% BTcP episodes still required under the administration of FBSF, which prompted the In a pilot study exploring the FBSF in dose proportional to opioid regimen for background analgesia [22], the percentage of rescue medication was reduced to 2.2%.…”

“…Pain intensity of the patient was further classified into three categories, as follows: 0-3 (mild intensity), 4-7 (moderate intensity), and 8-10 (high intensity). Satisfaction survey with FBSF analgesics was performed for each patient using a 5-point scale (poor, fair, good, very good, and excellent), derived from the Treatment Satisfaction Questionnaire for Medication (TSQM; [23]). The Pain and Satisfaction Survey Questionnaire used in this study is included in the Supplementary data.…”

“…Since high-intensity BTcP in cancer patients often requires high doses of analgesics, titration from low doses is often ineffective and time-consuming. Therefore, some studies suggest a dose proportionality strategy for fentanyl, as stepwise titration for effective pain relief is too slow in clinical practice, especially in advanced cancer patients in need of high-dose analgesia [21][22][23].…”

“…Several studies have demonstrated the dose proportionality of fentanyl released and absorbed following FBSF administration and its efficacy and safety in relieving BTcP with minimal adverse events [19,21,22,24]. Although the corresponding effective doses of FBSF has been established based on the around-the-clock (ATC) opioid regimens in oral morphine equivalence [23], it remains unclear how many cancer patients still require further dose titration to effectively and safely relieve BTcP and patient satisfaction with FBSF. Therefore, this prospective study aimed to evaluate whether dose-proportional FBSF could effectively and safely relieve BTcP episodes in cancer patients.…”