Takigawa, C., Goto, F., Tanda, S., Shima, Y., Yomiya, K., Matoba, M., . . . Eguchi, K. (2015). Breakthrough pain management using fentanyl buccal tablet (FBT) in combination with around-the-clock (ATC) opioids based on the efficacy and safety of FBT, and its relationship with ATC opioids: Results from an open-label, multi-center study in Japanese cancer patients with detailed evaluation. Japanese Journal of Clinical Oncology, 45, 67–74.

To assess the safety and efficacy of fentanyl buccal tablets (FBT) in breakthrough pain (BTP) management when given in combination with around-the-clock (ATC) opioids and to explore the influence of dose adjustments on breakthrough pain management

Before the maintenance phase, the FBT dose that was successful in providing sufficient pain relief without producing unacceptable adverse events was identified by titration. During the 12-week maintenance phase, the FBT dose was administered for BTP episodes. The successful dose ranged from 100–800 ug for patients who received an ATC opioid dose of 60–1,000 mg per day of oral morphine and from 50–800 ug for those who received from 30– < 60 mg per day of oral morphine equivalents. Patients were allowed to take additional supplemental medications including FBT when no pain relief was perceived by 30 minutes after FBT administration. FBT or ATC opioid doses could be changed if additional supplemental medications (including FBT) were frequently administered for BTP episodes or if there were five or more BTP episodes per day. FBT could be administered eight times per day for a maximum of six BTP episodes per day. Prestudy medications were given for the seventh or more BTP episode in a day of if the BTP episode occurred within four hours after a FBT administration.

• N = 82  
• AGE = 20 years and older
• MALES: 60%, FEMALES: 40%
• KEY DISEASE CHARACTERISTICS: Patients with cancer-related pain caused by solid or hematologic tumors and a life expectancy of three months or longer. Participants had to receive ATC opioid regiments to control their pain for at least one week prior to enrollment and had to experience one to four BTP episodes per day that had been controlled with supplemental medications.  
• OTHER KEY SAMPLE CHARACTERISTICS: Ability to evaluate pain in a self-recording diary; performance status grades 0–2 based on the Eastern Cooperative Oncology Group (ECOG) guidelines; exclusion included diseases or symptoms that could affect safety, oral conditions that could interfere with FBT application, clinical disorders that could compromise data collections (e.g., psychological), or concomitant medications including monoamine oxidase inhibitors, narcotic antagonist analgesics, narcotic antagonists and drugs administered for other clinical trials

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: 34 sites in Japan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Open-label study

• Pain intensity, pain relief, a global medication performance assessment, and an overall impression of FBT treatment were evaluated with each FBT administration.
• Safety included vital signs, arterial oxygen saturation, and the frequency and severity of each adverse event.

Forty-one patients completed the 12-week maintenance phase. A major reason for discontinuation was adverse events. No patients discontinued because of a lack of treatment efficacy. Treatment-related adverse events were reported by 37% of patients during the maintenance phase. The most common adverse events were somnolence (16%) and nausea (10.7%). Five deaths occurred during the study, none of which were related to FBT. Both the FBT and ATC opioid doses gradually increased over time from the beginning of the maintenance phase. The breakthrough FBT dose was changed in 42 patients (56.8%). The ATC opioid dose was changed in 50 patients (67.5%).

FBT has sustained analgesic effect and was well tolerated. Quality of life was reported to improve with stable or improved pain intensity, which was not clearly measured in this study. FBT was noted to be safe for long periods of time even with needed increase in its dose.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Single-arm trial; quality of life not measured; limited duration of study

Pain management is an important aspect of improving a patient's quality of life. Nurses play a key role in assisting patients and providing pain management medications and in teaching patients how to manage their pain when they are outside an inpatient facility. Additional agents need to be available to assist in optimal pain control.