Chang, J.T., Lin, C.Y., Lin, J.C., Lee, M.S., Chen, Y.J., & Wang, H.M. (2010). Transdermal fentanyl for pain caused by radiotherapy in head and neck cancer patients treated in an outpatient setting: A multicenter trial in Taiwan. Japanese Journal of Clinical Oncology, 40(4), 307–312.

To evaluate the effectiveness of transdermal fentanyl (TF) for pain management in patients with head and neck cancer receiving radiotherapy; to evaluate the effectiveness, safety, and long-term tolerability of TF after initial administration

Patients entered in the trial were instructed in the use of TF. Initial TF dose was 25 mcg/hour, and patches were replaced every three days. Dose was titrated upward as needed, in 25 mcg/hour increments. Patients requiring more than 50 mcg/hour were allowed to use multiple patches to achieve the required dose. Doses greater than 100 mcg/hour were used in exceptional circumstances only. As a treatment for breakthrough pain, patients received immediate-release morphine to be administered as needed, every 2–4 hours. Use of all rescue medications was recorded. Pain was measured by means of a questionnaire that was administered at study entry and after 7, 14, 28, 35, and 42 days. Amount of rescue analgesics and data about constipation, diarrhea, and use of laxatives and antidiarrheals were recorded by patients daily. Investigators summarized the data at each study visit.

• Initially, the sample was composed of 163 patients. The size of the sample at the end of the study was 108 patients.
• Mean patient age of the final sample was 53 years. Age range was 24–68 years.
• Of all patients, 9.2% were female and 90.8% were male.
• All patients had head and neck cancer and were receiving radiation therapy. Most were taking nonsteroidal anti-inflammatory drugs, codeine, and tramadol. Of all patients, 11% were taking morphine at the time of study entry, and 57.7% were receiving chemotherapy. The average radiation dose over 42 days was slightly under 7000 cGy. Initial pain scores for 44.2% of patients were equal to or greater than 7.

• Multisite
• Outpatient
• Taiwan

Prospective trial

• Visual analog scale (VAS), to measure pain
• Wisconsin Brief Pain Inventory (BPI), short version, to measure pain
• Five-point Likert scale (0 = fully awake, 4 = drowsy most of the time), to measure daytime drowsiness
• Five-point Likert scale (0 = no symptoms), 4 = very severe), to measure nausea or vomiting
• National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3, to measure adverse effects

• The most commonly used dose of TF was 25 mcg/hour at days 0, 7, 14, 21, and 28.
• Of patients treated by radiotherapy alone, 7% received a dose of TF that was larger than 25 mcg/hour. Of patients who also received chemotherapy, 34.8% required a dose larger than 25 mcg/hour.
• VAS pain scores declined in all patients, but authors reported no statistical significance. By day 42, VAS scores indicated no further decline in pain.
• Scores in each domain of the BPI improved after one week and on days 7 (p < 0.05) and 28 (p < 0.0001). BPI scores improved significantly.
• Of patients in the initial sample, 55 patients (34.4%) had dropped out by the second week of treatment. They dropped out because of side effects. Twenty additional patients (12.3%) did not complete the study because of interruption of radiotherapy due to sepsis, the fact that TF was no longer needed, grade 3–4 vomiting (23.9%), nausea (16.6%), somnolence (4.9%), or dizziness (4.9%)

Data suggest that TF can be effective and relatively easy to use, in an outpatient setting, for patients receiving radiotherapy; however, TF was accompanied by a high rate of severe side effects.

• The study had a risk of bias due to no appropriate control group.
• The study had a very high dropout rate due to side effects.
• Authors provide no statistical analysis over time of VAS score changes or other score changes.
• The reported findings related to side effects were confusing. Authors stated that, initially, 55 patients dropped out due to side effects and that another 20 patients did not complete the study. The actual prevalence and severity of side effects is unclear.

Additional research regarding various approaches to pain management, in the cited population, is needed.