Cai, Q., Huang, H., Sun, X., Xia, Z., Li, Y., Lin, X., & Guo, Y. (2008). Efficacy and safety of transdermal fentanyl for treatment of oral mucositis pain caused by chemotherapy. Expert Opinion on Pharmacotherapy, 9(18), 3137–3144.

To evaluate the efficacy and safety of transdermal fentanyl in the treatment of mucositis pain associated with chemotherapy

Transdermal fentanyl (TF) was administered at a rate of 25 mcg/hour for adult patients, including those who were opioid naive. In pediatric patients, TF was administered at 12.5 mcg/hour. Because of the delayed effect of TF, patients received IV or subcutaneous morphine to relieve pain during the 8–12 hours after application of the patch. The dose of TF was adjusted after the first 24 hours, according to pain score, until pain was controlled. (Control was defined as a score of 3 or less on the rating scale.) The dose of TF was increased in 25 mcg/hour increments or 12.5 mcg/hour increments, according to age group. Severe breakthrough pain was managed with IV or subcutaneous morphine. All subjects were routinely treated with oral hygiene and antiviral, antibacterial, or antifungal oral agents. The same clinician evaluated patients on the first day of chemotherapy and daily for approximately three weeks. The patient reported pain daily by citing a score on a numeric scale. Mucositis was evaluated, on a daily basis, in terms of National Cancer Institute (NCI) Common Toxicity Criteria (CTC). Study questionnaires were sent to all patients. Questionnaire data were recorded before treatment with TF and 2, 6, and 10 days later.

• The sample was composed of 32 patients.
• Median patient age was 40 years. Age range was 4–76 years.
• Of all patients, 56.3% were female and 43.7% were male.
• The most common diagnoses were non-Hodgkin lymphoma, neuroblastoma, nasopharyngeal cancer, breast cancer, and small-cell lung cancer. Other diagnoses were included in the sample. All patients had a pain score of 4 or higher at study entry. All patients were receiving chemotherapy.

• Multisite
• Outpatient
• China

Open-label prospective trial

• Numeric rating scale (NRS), to measure pain intensity
• NCI CTC, to measure mucositis and adverse events
• European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), to measure quality of life

• After chemotherapy, median time to onset of moderate oral mucositis was five days (range of days to onset was 1–16). 
• Prior to use of TF, median NRS pain score was 6. By day 3 and at days 5, 7, 10, and 15, NRS scores had improved significantly (p < 0.001), compared to NRS scores at baseline. By day 3 median NRS was 4; by day 10, median NRS was 2. Pain disappeared in 65.6% of subjects.
• Results as measured by the EORTC QLQ-C30 improved significantly (p < 0.001) in regard to appetite, mental status, sleep, fatigue, and daily life.
• A dose of 25 mcg/hour was sufficient to control mucositis pain in 75% of the sample. Of all patients, 18.8% developed nausea and vomiting, 15.6% reported dizziness, 15.6% reported stomach discomfort, 6.3% reported constipation, and 6.3% reported patch-related itching.
• No patients discontinued the drug because of toxicity.

In this study, transdermal fentanyl was effective in reducing pain and improving quality-of-life parameters in the sample specified. Transdermal fentanyl was associated with a relatively low prevalence of adverse effects.

• The study had a small sample, with fewer than 100 patients.
• Authors did not state whether any patients required use of medication for breakthrough pain.
• Authors did not report the prevalence of adverse effects by severity.
• The number of pediatric patients versus adult patients was not stated. The means by which authors measured the pain and quality of life of very young patients (some as young as 4 years old) was not reported.
• Other mechanisms for the management of oral mucositis, which could be expected to influence pain, were not controlled or fully described.

Authors noted the delay of onset with TF opioid use. This delay suggests that TF therapy begin before onset of significant levels of pain. Further well-designed studies of TF, in adults and children, are needed.