Shimoyama, N., Gomyo, I., Teramoto, O., Kojima, K., Higuchi, H., Yukitoshi, N., . . . Shimoyama, M. (2015). Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain. Japanese Journal of Clinical Oncology, 45, 189–196. 

To test the efficacy and safety of oral fentanyl in doses estimated from basal oral morphine for breakthrough pain

There was an initial observation phase in which breakthrough pain episodes were evaluated. Patients who showed effects from oral morphine entered the investigation phase. The investigation phase included three periods in which two different doses of fentanyl orally disintegrating tablets (FTs) and active controls were investigated in a random order. The dose of the FTs was determined by a conversion ratio of 1:25 for low-dose morphine and 1:50 for high-dose morphine in the observation phase. There were three episodes of breakthrough pain in each period of the investigation. FTs were given twice, and the placebo was given once. Oral morphine was used in the observation period and was given as an active control. Some studies have shown that effective doses of FTs for breakthrough pain did not correlate to round-the-clock opioid doses.

• N = 47  
• MEAN AGE = 59.1 years (range = 37–80 years)
• MALES: 60.8%, FEMALES: 39.2%
• KEY DISEASE CHARACTERISTICS: Various tumor types with lung cancer most common
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were receiving daily opioid analgesics and oral morphine to treat breakthrough pain at least once every two days.

• SITE: Single site  
• SETTING TYPE: Not specified    
• LOCATION: Japan

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

Randomized, crossover, double-blinded, placebo-controlled trial with a nonblinded active drug

• Visual Analog Scale (VAS) for pain at 30 and 60 minutes during breakthrough episodes

FTs were better than a placebo for all patients (p < 0.02) and better than the oral morphine control (p < 0.001) at 30 minutes. At 60 minutes, FTs also were better than a placebo (p < 0.001). Nine subjects had adverse reactions. The most common reactions were constipation, nausea, and somnolence. One had nausea and vomiting, and one experienced respiratory depression. A temporary suspension of the investigation drug was initiated in both of these cases.

The findings of this study demonstrated that the method of dose determination used here was safe in the majority of cases, more effective than a placebo, and as effective as oral morphine for breakthrough pain.

• Small sample (< 100)
• Subject withdrawals ≥ 10%

The dose of FTs for breakthrough pain is usually determined by titrating effective doses over a period of time. During titration, the patient may have less than optimal pain control. This study provided a method of dose determination that may be useful and more timely.