Kongsgaard, U.E., Eeg, M., & Greisen, H. (2014). The use of Instanyl^® in the treatment of breakthrough pain in cancer patients: A 3-month observational, prospective, cohort study. Supportive Care in Cancer, 22, 1655–1662.

To evaluate Instanyl^® for breakthrough pain in patients with cancer in real-life settings

This study followed adult patients with cancer receiving Instanyl^® in seven countries at 61 centers. The Brief Pain Inventory Short Form (BPI) and patient Treatment Satisfaction Scale (TSS) questionnaires were used to assess patient satisfaction with pain management. Descriptive statistics of the patient population were also collected. The Instanyl^® doses received by patients were 50, 100, and 200 micrograms, and data were collected at three time points: baseline, week 4, and week 13.

• N = 309 overall analysis (107 completed study)  
• AVERAGE AGE = 60 years
• MALES: 56%, FEMALES: 44%
• KEY DISEASE CHARACTERISTICS: Metastases present

• SITE: Multi-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Multiple study centers in Norway, Denmark, France, Greece, Ireland, Sweden, and the United Kingdom

• PHASE OF CARE: Mutliple phases of care
• APPLICATIONS: Elder care, adult care, palliative care

Observational prospective cohort study

The primary outcome variables were success of titration, measured by whether maintenance dose level was achieved, and the dose level of Instanyl^® (maintenance dose). The secondary outcome variables measured were changes in maintenance dose and the level of background pain medication, severity and impact of pain on daily life (assessed by the BPI), and satisfaction with current pain medicine (assessed by the TSS). The BPI and TSS were only used in the United Kingdom and in France and were assessed at baseline and during week 4. Adverse drug reactions were measured as well as reasons for and time to Instanyl^® termination.

The successful titration of Instanyl^® to a maintenance dose was achieved in 84.5% of patients. There was a difference noted between different countries with successful titration rates highest in Greece and Norway and lowest in France and the United Kingdom. The majority of the patients who were successfully titrated achieved this with 50 micrograms of fentanyl, which was the lowest dose. Most patients showed no change in the maintenance dose strength throughout the study even though disease progression was expected. 49.8% of patients were successfully titrated at 50 micrograms, the lowest dose. Treatment was followed to the duration of 13 weeks. In 4.5% of patients, termination was due to lack of efficacy; in 2.3% it was due to adverse effects; and in 7.1% it was due to the inability to successfully titrate the medication. Patients' worst-pain scores, pain severity, and pain interference with activities declined significantly within the first four weeks (p < .001).

The rate of successful titration and pain management using Instanyl^® was high in this study, and successful titration was often achieved with the lowest possible dose of Instanyl^®. Patients were more satisfied with their pain management and had reductions in pain severity, worst-pain score, and pain interference with daily activities.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Subject withdrawals ≥ 10% 
• Other limitations/explanation: Only about 35% of patients completed the study, there was a lack of a comparison arm, and adverse drug reactions were not reported.

This study adds to the body of evidence regarding the efficacy of opioid nasal spray for breakthrough pain. The authors suggest that patients who did not respond were likely those for whom titration to full dosage was not achieved. Nurses need to be aware of full dosage needs for efficacy. There continues to be a lack of evidence regarding the long-term effects and any potential adverse effects on the nasal cavity for this medication type.