Abstract
Purpose
Breakthrough pain (BTP) is a transient exacerbation of pain occurring in a patient with chronic, persistent pain. The most common type is incident pain that is mostly related to bone metastases. The oral mucosa is an attractive route for drug delivery. Sublingual fentanyl preparations are a very attractive agent in controlling attacks of BTP due to its rapid absorption through the oral mucosa. Non-steroidal anti-inflammatory drugs (NSAIDs) play a key role as a first step in treatment of cancer pain; piroxicam sublingual formulations could be a useful alternative in controlling incident pain. Our study hypothesis is to evaluate the efficacy of sublingual fentanyl versus oral piroxicam fast-dissolving tablets in patients with incident pain and its impact on functional status.
Patients and methods
A cohort of 100 adults of both genders suffering from bone metastases. Patients were assigned to receive either sublingual fentanyl tablet (group 1) or oral piroxicam fast-dissolving tablets (group 2). The pain intensity reduction on a 0–10 visual analog scale (VAS), frequency of BTP attacks, and onset of pain relief. Secondary end points included the functional interference items of the Brief Pain Inventory (BPI).
Results
There is no significant difference between the two groups regarding the patients’ demographics. Significant decline of the VAS in each group in comparison to the pretreatment values (p = 0.001). Non-significant changes of the VAS, duration of pain attacks, and number of rescue doses in comparing both groups were measured. There was significant reduction in group 2 BPI regarding the relation with others, sleep pattern and enjoyment of life parameters at 2 and 4 weeks (p = 0.001).
Conclusion
Our study demonstrated that oral piroxicam fast-dissolving tablet is an analgesic alternative to sublingual fentanyl in patients with bone metastasis to control incidental BTP attacks with more favorable cost-benefit values.
Similar content being viewed by others
References
Margarit C, Juliá J, López R, Anton A, Escobar Y, Casas A, Cruz JJ, Galvez R, Mañas A, Zaragozá F (2012) Breakthrough cancer pain– still a challenge. J Pain Res 5:559–566
Mishra S, Bhatnagar S, Chaudhary P, Pratap S, Rana S (2009) Breakthrough cancer pain: review of prevalence, characteristics and management. Indian Journal of Palliative Care 15(1):14–18
Patel VF, Liu F, Brown MB (2011) Advances in oral transmucosal drug delivery. J Control Release 153:106–116
Lennernäs B, Frank-Lissbrant I, Lennernäs H, Kälkner KM, Derrick R, Howell J (2010) Sublingual administration of fentanyl to cancer patients is an effective treatment for breakthrough pain; results from a randomized phase II study. Palliat Med 24:286–293
Omoti AE, Omoti CE (2007) Pharmacological strategies for the management of cancer pain in developing countries. Pharm Pract 5(3):99–104
Kuo KL, Saokaew S, Stenehjem DD (2013) The pharmacoeconomics of breakthrough cancer pain. J Pain Palliat Care Pharmacother 27(2):167–175
Mercadante S, Radbruch L, Caraceni A, Cherny N, Kaasa S, Nauck F, Ripamonti C, De Conno F (2002) Episodic (breakthrough) pain consensus conference of an expert working group of the European Association for Palliative Care. Cancer 94:832–839
Mercadante S, Villari P, Ferrera P, Casuccio A (2004b) Optimization of opioid therapy for preventing incident pain associated with bone metastases. J Pain Symptom Manag 28:505–510
San K, Carla MB, Sheri LD, Jeff S, Tito RM, Charles SC (2004) Validity of the brief pain inventory for use in documenting the outcomes of patients with noncancer pain. Clin J Pain 20(5):309–318
Zhang H, Zhang J, Streisand JB (2002) Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 41:661–680
Payne R (1997) Mechanisms and management of bone pain. Cancer Supplement 80(8):1608–1613
Yalcin S, Altundag K, Asil M, Tekuzman G (1998) Sublingual piroxicam for cancer pain. Med Oncol 15:137–139
Gَmez-Batiste X, Madrid F, Moreno F, Gracia A, Trelis J, Nabal M et al (2002) Breakthrough cancer pain: prevalence and characteristics in patients in Catalonia, Spain. J Pain Symptom Manag 24:45–52
Davies AN, Vriens J, Kennett A, McTaggart M (2008) An observational study of oncology patients’ utilisation of breakthrough pain medication. J Pain Symptom Manag 35(4):406–411
Janecki M, Janecka J (2011) Breakthrough pain in patients with chronic cancer pain followed by palliative care and pain clinic physicians — an observational study. Palliat Med 10(1):29–34
Rauck RL, Tark M, Reyes E, Hayes TG, Bartkowiak AJ, Hassman D, Nalamachu S, Derrick R, Howell J (2009) Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Curr Med Res Opin 25(12):2877–2885
Smith HS (2013) Considerations in selecting rapid-onset opioids for the management of breakthrough pain. J Pain Res 6:189–200
Chwieduk CM, McKeage K (2010) Fentanyl sublingual: in breakthrough pain in opioid-tolerant adults with cancer. Drugs 70(17):2281–2288
Überall MA, Müller-Schwefe GH (2011) Sublingual fentanyl orally disintegrating tablet in daily practice: efficacy, safety and tolerability in patients with breakthrough cancer pain. Curr Med Res Opin 27(7):1385–1394
Lister N, Warrington S, Boyce M, Eriksson C, Tamaoka M, Kilborn J (2011) Pharmacokinetics, safety, and tolerability of ascending doses of sublingual fentanyl, with and without naltrexone, in Japanese subjects. J Clin Pharmacol 51(8):1195–1204
Jandhyala R, Fullarton JR, Bennett MI (2013) Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials. J Pain Symptom Manag 12:1–8
Shimoyama N, Gomyo I, Teramoto O, Kojima K, Higuchi H, Yukitoshi N, Ohta E, Shimoyama M (2015) Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain. Jpn J Clin Oncol 45(2):189–196
Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G (2009) The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain 13:331–338
Acknowledgments
The authors would like to thank the hospital pharmacist and the nursing staff of the pain clinic who participated in the study; in addition, we thank Prof Ibrahem Al-kabbash, our study statistician.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The study was approved by an Investigational Review Board of the Faculty of Medicine, Tanta University; an informed written consent was obtained from all patients participating in the study. This study was registered in the clinical trials registry (clinicaltrials.gov) with a unique identification number NCT02382653.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Yousef, A.A., Alzeftawy, A.E. The efficacy of oral piroxicam fast-dissolving tablets versus sublingual fentanyl in incident breakthrough pain due to bone metastases: a double-blinded randomized study. Support Care Cancer 27, 2171–2177 (2019). https://doi.org/10.1007/s00520-018-4469-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00520-018-4469-6