When used as a rinse, doxepin, a tricyclic antidepressant, reduces oral mucositis (OM) in patients who receive radiation therapy (RT) for head and neck cancer, according to research presented at the American Society for Radiation Oncology’s (ASTRO’s) 54th Annual Meeting.

The multi-institution, randomised, double-blind, placebo-controlled, phase III trial, with a cross-over phase, assessed the efficacy of doxepin oral rinse versus placebo for the treatment of OM associated with RT.

The study included 140 patients between December 2010 and May 2012 who received RT for their head and neck cancer (> 50.0 Gy) and which involved more than one-third of the oral cavity.

Throughout the study, patients completed a numerical, analog pain questionnaire to rate their OM pain on a scale of one to 10.

The patients included in this study all reported OM pain scores above four prior to the study protocol to receive doxepin or placebo.

On the first day of the protocol, patients received a single, blinded dose of doxepin rinse or placebo and then crossed over to the opposite study group on a subsequent day.

Results indicate that the addition of doxepin significantly decreased pain, which was measured by the area under the curve (AUC) on the pain scale over time. Patients who received doxepin reported a reduction in pain to a -9.1 vs. -4.7 for those who received the placebo.

Analysis of the crossover data revealed similar findings, with an AUC score of -7.9 in the doxepin group vs. -5.6 in the placebo group.

Doxepin was well tolerated, but patients reported increased stinging/burning with doxepin compared to the placebo (mean pain score of 3.7 for doxepin vs. 1.1 for placebo), unpleasant taste (mean unpleasant taste at five minutes of 2.9 for doxepin vs. 1.6 for placebo) and greater drowsiness (mean drowsiness score of 3.9 for doxepin vs. 2.8 for placebo). Sixty-four percent of patients elected to continue doxepin after the study was completed.

The study was conducted through the Alliance for Clinical Trials in Oncology (NCCTG/CALGB/ACOSOG), and patients received doxepin as an oral rinse and spit at a dosage of 25 mg in 5 ml water. The pain questionnaire was administered at baseline and at five, 15, 30, 60, 120 and 240 minutes after receiving the rinse, and patients were given the option to continue doxepin after completing the study.

The study evaluated total OM pain reduction as measured by the AUC beginning on the first day of treatment. The baseline-adjusted AUC between the two treatment groups was compared using the Wilcoxon rank-sum test. Baseline factors were evenly distributed across arms.

“Doxepin rinse has previously been proven to be a well-tolerated treatment for mouth pain due to radiation and chemotherapy treatment,” said Robert C. Miller, MD, lead author of the study and a radiation oncologist at the Mayo Clinic in Rochester, Minn. “Radiation for head and neck cancer often causes painful mouth sores and oral mucositis. Our study validates doxepin rinse as an effective way to alleviate oral pain and sets a new standard of care.”

The abstract, “N09C6 (Alliance) - A Phase III, Randomized Double-Blind Study of Doxepin Rinse versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy with or without Chemotherapy,” was presented in detail during the plenary session at ASTRO’s 54th Annual Meeting.

Source: ASTRO