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

Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

Chiang YH ，Lien CT ，Su WH ，Yen TY ，Chen YJ ，Lai YL ，Lim KH ，Dai KY ，Chung HP ，Hung CY ，Leu YS ... -  《BMC Palliative Care》

Fentanyl buccal tablet for breakthrough cancer pain in clinical practice: results of the non-interventional prospective study ErkentNIS.

Masel EK ，Landthaler R ，Gneist M ，Watzke HH ... -  《-》

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

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. This study aimed to assess the feasible dose range of FBSF required for Taiwanese population. 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. 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.

Chiou TJ ，Chao TC ，Chao TY ，Huang JS ，Chang YF ，Wang CH ... -  《Cancer Reports》

Proportional dose of rapid-onset opioid in breakthrough cancer pain management: An open-label, multicenter study.

Yen TY ，Chiou JF ，Chiang WY ，Su WH ，Huang MY ，Hu MH ，Wu SC ，Lai YL ... -  《-》

Efficacy and safety of fentanyl inhalant for the treatment of breakthrough cancer pain: a multicenter, randomized, double-blind, placebo-controlled trial.

Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.

Lin R ，Song B ，Li N ，Rong B ，Bai J ，Liu Y ，Wang W ，Liu A ，Luo S ，Liu B ，Cheng P ，Wu Y ，Li Y ，Yu X ，Liu X ，Dai X ，Li X ，Liu D ，Wang J ，Huang Y ... -  《BMC Palliative Care》