Fentanyl Pectin Nasal Spray reduces breakthrough cancer pain intensity compared with placebo in people taking at least 60 mg daily oral morphine or equivalent
- Correspondence to Carol P Curtiss
Master of Science in Pain Research, Education and Policy (MSPREP) Program, 73 James Street, Greenfield, MA 01301, USA; carol.
Implications for nursing practice
▪ Breakthrough pain is a significant problem for people with cancer.
▪ Patterns of breakthrough pain are often different from the pharmacokinetics of immediate release oral analgesics.
▪ Matching patterns of breakthrough pain with medications that work within the timeframe of breakthrough pain may improve breakthrough pain management.
▪ A comprehensive assessment includes evaluating breakthrough pain separately from persistent pain, using similar strategies for screening and assessing both types of pain.
▪ Fentanyl Pectin Nasal Spray (FPNS) provides an additional option to manage breakthrough cancer pain (BTCP).
▪ Patient education regarding the correct use of medications for persistent and breakthrough pain and the appropriate use of novel routes of administration is important for optimal analgesic medication efficacy and safety.
Implications for research
▪ Additional research on assessing and managing breakthrough pain is important to identify appropriate treatment options.
▪ Novel routes of medication administration for breakthrough pain may provide new insight into the management of this distressing and complex type of pain.
▪ Research regarding patient adherence and satisfaction with new routes of administration can guide nursing practice and patient education.
▪ Research regarding costs, patient access to new medications for breakthrough pain and effects on quality of life may promote development of and access to new products.
The prevalence of breakthrough pain from cancer ranges from 30–40% at diagnosis to 70–80% in people with advanced disease. Breakthrough pain occurs on a background of stable persistent pain. Episodes often have rapid onset and are unpredictable.1 Traditionally, short-acting oral analgesics are used, but new routes of administration allow clinicians to more effectively match the onset, peak and duration of an analgesic to the timing of breakthrough episodes. Transmucosal fentanyl has an onset similar to fentanyl via intravenous injection and may improve pain management for those with rapid onset or unpredictable breakthrough pain. Teaching patients regarding correct use, safety and storage of breakthrough pain medications is an important nursing role.
The primary end point of this study is determination of the efficacy of FPNS compared with placebo in the treatment of BTCP in patients receiving regular opioid therapy. Secondary objectives were to demonstrate onset of action, time to clinically meaningful pain relief, safety, tolerability and patient acceptability.
This multicentre, randomised, placebo-controlled, double-blinded, multiple cross-over study was conducted at 36 centres in the USA, Costa Rica and Argentina. The maximum study duration for an individual patient was 8 weeks. Participants included 113 adults with cancer (53.1% male) who were receiving a total daily dose equivalent to or greater than 60 mg oral morphine a day for background pain and had one to four episodes of moderate to severe BTCP daily. Mean age was 53.8±1.1. Patients entered an open-label dose titration phase to determine the individual dose that would control BTCP. Those who found an effective dose entered the double-blind phase where a total of 10 BTCP episodes per patient were treated with either FPNS (seven episodes) or placebo (three episodes). Patients and all personnel involved in the study were blinded to the medications used. If needed, rescue medication was allowed after 30 min.
Data collection included the following measurements: (1) electronic diaries measuring baseline pain intensity (0–10 scale); (2) pain intensity and pain relief (0–4 scale) at 5, 10, 15, 30, 45 and 60 min; (3) satisfaction (1–4 scale); (4) ease of use and convenience (4-point scale); (5) visual nasal inspection by a physician at the beginning and end of treatment; (6) subjective nasal assessment by the patient using a 10-item questionnaire; and (7) patient-averaged summed pain intensity difference after 30 min (SPID30). SPID30 is commonly used to evaluate the efficacy of medications for BTCP.
Of the 113 patients enrolled in the titration phase, 83 (73.5%) identified an effective and tolerable dose of FPNS and entered into the double-blind phase of the study, with 91.6% completing the study. FPNS was efficacious for pain, as indicated by the primary end point (SPID30) compared with placebo and at each time point from 10 to 60 min after dosing. In addition, mean pain intensity scores, pain relief scores and total pain relief scores were statistically significant from 10 min and at all points to 60 min. Thirty-three per cent of episodes had meaningful pain relief within 10 min and 51%, within 15 min. Overall, 90.6% of episodes treated with FPNS versus 80% of episodes treated with placebo did not require additional rescue medication within 60 min. Treatment-related adverse events were similar to those expected with opioid therapy. Objective clinical assessment of the nasal mucosa showed no changes.
This study is the first to evaluate the efficacy, safety and tolerability of fentanyl as a nasal spray for BTCP. The study design is similar to other studies evaluating the efficacy, safety and tolerability of transmucosal fentanyl. The end points are those required in some countries for regulatory approval of new products. Although data regarding reliability and validity of the measurement scales are not included, these scales are commonly used, and reliability and validity are published. The findings suggest that intranasal fentanyl provides an additional option to match the timing of analgesia to individual patterns of BTCP. That 80% of episodes treated with a placebo did not require rescue medication within 60 min supports similar results in other studies of medications for BTCP.2 The authors argue this may be related to reductions in the anticipation of pain. This study serves as a reminder that comprehensive individual patient assessment of background pain and breakthrough pain must guide treatment selection for optimum cancer pain management.
Competing interests CPC is on the Advisory Board and Speakers Bureau for Meda Pharmaceuticals.