0804184.pdf

Study Purpose

To determine the efficacy and tolerability of intranasal fentanyl spray (INFS) in the treatment of cancer-related breakthrough pain

Intervention Characteristics/Basic Study Process

Eligible patients went through an open dose-titration phase to determine an effective individual dose of the study drug. In the double-blind phase, patients were given 10 “blinded” bottles containing either the determined dose of INFS or placebo. The bottles were in a randomly assigned sequence. Each patient self-administered a maximum of four doses per day. If relief was inadequate at 30 minutes or if a separate episode of breakthrough pain occurred within a four-hour period, patients could take their usual rescue medication for analgesia. After each treatment episode, subjects recorded relief scores at timed intervals and rated overall satisfaction by means of an electronic diary. Self-reported adverse events were recorded throughout the study, and the study clinician directly assessed nasal condition at the beginning and end of the study.

Sample Characteristics

Seventy-six patients completed the study.
Mean patient age was 53.8 years (SD = 11.6 years).
Authors did not report information about the gender of participants.
Patients were not receiving active chemotherapy or radiation therapy and did not have unstable clinical conditions or rapidly escalating or uncontrolled pain.
The mean baseline pain-intensity score was 6.89 (SD = 1.7) across INFS-treated episodes and 6.96 (SD = 1.83) for placebo-treated episodes.

Setting

Multisite
Outpatient
The state of Georgia, United States

Study Design

Randomized double-blind, placebo-controlled multiple-crossover study

Measurement Instruments/Methods

Numeric pain-intensity scale (0 = no pain, 10 = worst possible pain)
Five-point pain-relief scale
Nasal assessment questionnaire, to identify of nasal symptoms

Results

Of patients in the open label-titration phase, 72.8% found an effective and tolerable dose of IFNS. Of patients who withdrew from the titration phase, 11.4% withdrew because of adverse events or lack of efficacy.
The analgesic effect of INFS was consistently better than that of placebo at all time points measured. At 15 minutes from the beginning of the pain episode, 73% had an observed pain-reduction effect (P < 0.0001 compared to placebo). Reduction of pain in INFS episodes was clinically meaningful (pain-reduction score ≥ 2-point reduction) at all time points (p < 0.0001 versus placebo)
Of all episodes of breakthrough pain treated with INFS, 90% did not require additional rescue medication. Of all episodes of breakthrough pain treated with placebo, 80% required rescue medication (p < 0.001).
Speed of relief was better with INFS than with placebo (p < 0.0001).
The most common side effects of INFS were vomiting, nausea, dizziness, epistaxis, nasopharyngitis, somnolence, and headache. Most nasal events were mild.

Conclusions

INFS is effective for the relief of breakthrough cancer pain for some patients and, as administered in this study, is not associated with severe and prevalent adverse effects.

Limitations

The study has a small sample size, with fewer than 100 patients.
The duration of the study was short, so efficacy and tolerability over a long term are unknown.
The study comprised a relatively healthy population, and patients were not under treatement. As a result, the results of this study may not be applicable to other patients and other situations.
The length of time a patient had chronic pain prior to study participation is not provided, and the range of regular opioid doses is not provided. These factors may have effects.
The fact that the fentanyl was associated with more taste disturbance than was placebo suggests that patients may not have been unaware of the drug they were using.

Nursing Implications

For the short term, INFS is effective for the management of breakthrough pain episodes for some patients with cancer. Nurses should be aware of the need for assessment of nasal symptoms with INFS use. The fact that slightly more than 20% of patients did not find an effective and tolerable dose of INFS is a reminder that effective pain management, which includes management of breakthrough episodes, needs to be highly individualized to be effective. INFS appears to be a useful part of the set of strategies to manage cancer-related pain. Despite strong evidence from this study, in regard to the immediate effect of INFS, research has not ascertained the effects of long-term INFS use.