Doxepin oral rinse significantly improved oral mucositis in patients treated with radiation therapy for head and neck cancer according to results of a phase III trial presented at the 54th Annual Meeting of the American Society for Radiation Oncology (ASTRO) in Boston. However, the improvement was modest.
Lead author of the study, Robert C. Miller, MD, of the Mayo Clinic in Rochester, Minnesota, explained that radiation-induced oral mucositis pain is a significant problem that does not always resolve with narcotics and traditional mouth rinses. Doxepin is a tricyclic antidepressant approved in the United States for depression, anxiety, and moderate pruritus. Smaller studies suggested that doxepin reduces mucositis pain in patients with cancer when used as a mouth rinse. The study presented at the ASTRO meeting establishes the drug’s effectiveness in alleviating oral mucositis pain.
“Our study validates doxepin rinse as an effective way to alleviate oral pain and sets a new standard of care,” Dr. Miller said. “This is important for two reasons: The first is that oral mucositis pain is often poorly controlled, and this medication can help us do a better job of reducing patient discomfort. The second is that patients can become dehydrated and undernourished during the weeks of head and neck radiation due to their mucositis keeping them from eating, and this can interrupt their cancer therapy. By treating their pain more effectively, we reduce the risk of an interruption in their cancer treatment that might reduce its effectiveness.”
N09C6 was a double-blind, randomized, placebo-controlled trial of 140 patients with head and neck cancer who had oral mucositis pain scores above 4 (out of 10). Patients with head and neck cancer were enrolled between December 2010 and May 2012 and treated with radiation at doses above 50 Gy involving more than one-third of the oral cavity. Patients assigned to doxepin used an oral rinse at a dosage of 25 mg in 5 mL of water for 1 minute on day 1; patients then crossed over to the other treatment arm on day 2. Continued treatment with doxepin was allowed on an as-needed basis.
Pain was measured by the area under the curve (AUC) on a pain scale over time. On day 1, doxepin-treated patients reported a pain reduction to –9.1 vs –4.7 for placebo recipients (P = .0003). Crossover data from day 2 showed similar findings, with an AUC pain score of –7.9 in the doxepin group vs –5.6 in the placebo group (P = .009).
Doxepin was well tolerated, but was associated with more stinging and burning (mean pain score of 3.7 for doxepin vs 1.1 for placebo) as well as an unpleasant taste (mean unpleasant taste score at 5 minutes of 2.9 for doxepin vs 1.6 for placebo), and caused greater drowsiness (mean drowsiness score of 3.9 for doxepin vs 2.8 for placebo). During the optional continuation phase, the majority of patients (64%) elected to continue doxepin. ■
Disclosure: Dr. Miller is on the scientific advisory board of Tekcapital.
1. Miller RC, Leenstra J, Qun R, et al: N09C6 (Alliance): A phase III, randomized double-blind study of doxepin rinse versus placebo in the treatment of oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy. 54th ASTRO Annual Meeting. Abstract LBA1. Presented October 29, 2012.
Formal discussant of this trial, Paul Harari, MD, University of Wisconsin School of Medicine and Public Health, Madison, commended the N09C6 investigators for conducting a randomized controlled phase III trial on symptom relief.
“Most phase III trials are conducted to evaluate a new cancer...