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The need for rapid intervention during breakthrough pain episodes renders management with oral opioids suboptimal, although several opioid interventions have been explored.4 General anesthesia precludes patient participation in radiotherapy procedures.3 Several rapid-analgesia interventions have been studied, including intranasal opioids, inhaled opioids, parenteral morphine delivery, and the investigational use of sublingual ketamine with local anesthetics.4

Oral (buccal) fentanyl, a fast-acting analgesic also studied for managing breakthrough cancer pain, has been found to be superior to oral morphine and other opioid medications, particularly among patients who developed opioid-tolerant pain—notably, patients with prostate or breast cancer are frequently not opioid-tolerant.1,4

Fentanyl pectin nasal spray (FPNS) similarly provides faster pain relief and higher levels of patient-reported satisfaction with pain relief than other opiates, such as immediate-release morphine sulfate, both in radiation-procedure and radiation-induced acute oral mucositis settings.7-11 The rapid onset of pain relief associated with FPNS makes it appealing for the treatment of both unanticipated and predictable pain in the radiotherapy setting.1,3 Case studies suggest patient-reported intensity of breakthrough cancer pain can be markedly diminished during radiotherapy, from a 7 or 8 on a 10-point scale—10 representing pain as bad as can be imagined—down to a 2.1

A recent study involving 27 patients with advanced cancer, most of whom (n = 20) had bone metastases, who experienced moderate-to-severe breakthrough cancer pain associated with routine radiotherapy procedures, found patient-reported breakthrough pain scores were reduced by 50% or more at 15.5 minutes after administration of FPNS 100 to 400 µg.3 Pain relief was reported at 3 to 15 minutes after FPNS administration.3

FPNS was well-tolerated, with only 1 patient discontinuing participation in the study because of intense dizziness and nausea. Overall, the researchers found “a gain in health-related quality of life, decreasing the pain and economic cost per patient.”3

“FPNS offers rapid absorption and analgesia,” reported Isabel Prieto, MD, lead author of the study, and colleagues at the Department of Radiation Oncology, Fundación Jiménez Díaz University in Madrid, Spain.3 “It is particularly efficient and well accepted by radiotherapy patients. Such relief allows the necessary procedures to be completed accurately, without additional needless suffering for patients, and maintaining radiotherapy department productivity.”

The researchers called for clinical trials to formally compare the tolerability and efficacy of FPNS and other treatments for breakthrough cancer pain.3


1. Bell BC, Butler EB. Management of predictable pain using fentanyl pectin nasal spray in patients undergoing radiotherapy. J Pain Res. 2013;6:843-848. doi:10.2147/JPR.S54788.

2. Prieto I, Pardo J, Marin J, et al. Fentanyl pectin nasal citrate to control breakthrough pain provoked by routine radiation therapy procedures and maneuvers in advanced cancer patients. Int J Radiat Oncol Biol Phys. 2013;87(2):S566.

3. Prieto I, Pardo J, Luna J, et al. Facilitation of accurate and effective radiation therapy using fentanyl pectin nasal spray (FPNS) to reduce incidental breakthrough pain due to procedure positioning. Scand J Pain. 2016;11:52-58. doi:10.1016/j.sjpain.2015.12.001.

4. Davis MP. Recent development in therapeutics for breakthrough pain. Expert Rev Neurother. 2010;10(5):757-773. doi:10.1586/ern.10.41.

5. Pignon T, Fernandez L, Ayasso S, Durand MA, Badinand D, Cowen D. Impact of radiation oncology practice on pain: a cross-sectional survey. Int J Radiat Oncol Biol Phys. 2004;60(4):1204-1210.

6. Janjan N. Do we need to improve pain management in the radiation oncology department? Nat Clin Pract Oncol. 2005;2(3):130-131.

7. Torres LM, Revnic J, Knight AD, Perelman M. Relationship between onset of pain relief and patient satisfaction with fentanyl pectin nasal spray for breakthrough pain in cancer. J Palliat Med. 2014;17(10):1150-1157. doi:10.1089/jpm.2014.0089.

8. Moleron R, Cerezo L, Ruiz A, Hervas A, Mañas A, De la Torre A. Ability of intranasal transmucosal fentanyl in pectin to prevent breakthrough pain episodes in patients with radiation-induced oropharyngeal mucositis. Eur J Cancer. 2015;51(suppl3):S233.

9. Bossi P, Locati L, Bergamini C, et al. Fentanyl pectin nasal spray as treatment for incident predictable breakthrough pain (BTP) in oral mucositis induced by chemoradiotherapy in head and neck cancer. Oral Oncol. 2014;50(9):884-887. doi:10.1016/j.oraloncology.2014.06.013.

10. Portenoy RK, Burton AW, Gabrail N, Taylor D; Fentanyl Pectin Nasal Spray 043 Study Group. A multicenter, placebo-controlled, double-blind, multiple-crossover study of Fentanyl Pectin Nasal Spray (FPNS) in the treatment of breakthrough cancer pain. Pain. 2010;151(3):617-624.

11. Fallon M, Reale C, Davies A, et al; Fentanyl Nasal Spray Study 044 Investigators Group. Efficacy and safety of fentanyl pectin nasal spray compared with immediate-release morphine sulfate tablets in the treatment of breakthrough cancer pain: a multicenter, randomized, controlled, double-blind, double-dummy multiple-crossover study. J Support Oncol. 2011;9(6):224-231.