Mercadante, S., Vellucci, R., Cuomo, A., Adile, C., Cortegiani, A., Valle, A., . . . Casuccio, A. (2015). Long-term efficacy and tolerability of intranasal fentanyl in the treatment of breakthrough cancer pain. Supportive Care in Cancer, 23, 1349–1354.

To assess the tolerability and effectiveness of intranasal fentanyl (INFS) for breakthrough pain in opioid-tolerant patients over six months

Patients receiving INFS for breakthrough pain were recruited and data were obtained from patients via survey and clinical records. Patients were followed at three months and six months in person, and data were obtained monthly for six months.

• N = 34 (three months), 12 (six months)
• MEAN AGE = 64.8 years (SD = 12.7 years)
• MALES:  86.7%, FEMALES: 13.3%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types 
• OTHER KEY SAMPLE CHARACTERISTICS: Mean opioid doses for background analgesia ranged from 111–180 mg per day, and mean INFS doses ranged from 87–119 mcg.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Italy

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

Observational cohort

• Four-point scale for general impression of efficacy from 1 (poor) to 5 (excellent)
• Adverse reactions graded from 0 (none) to 3 (severe)
• Quality of sleep graded from 0 (disturbed) to 3 (very good)

No patients discontinued treatment because of adverse effects. The high drop-out rate over time was caused by death and loss to follow-up. Only minor adverse effects were reported, and they were considered to be related to the opioid therapy used for background pain. Overall, 22% of participants had moderate adverse effects at one month, and 11% had effects at four months. At other time periods, less than 6% had any adverse effects. The most frequent adverse effect was drowsiness. Most patients were receiving buprenorphine, transdermal fentanyl, or oxycodone for background pain. Sleep scores improved significantly over the first four months (p < 0.05). Efficacy scores improved over the first three months overall (p = 0.0005). After three months, the majority of patients reported efficacy levels at 4 or 5.

The findings of this study suggested that INFS for breakthrough pain was well-tolerated and effective for several months.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: High loss to follow-up with resulting low sample sizes at follow-up periods; measurement methods not validated or shown to be reliable; methods of data collection not clear; not clear if patients were directly surveyed or data were obtained from medical records or provider evaluations

There is little information on the long-term efficacy and side effects of INFS for breakthrough pain. This study provided some information in this area, suggesting that INFS was well-tolerated and continued to be effective for the majority of patients in a four- to six-month timeframe.