Nick Mulcahy

October 30, 2012

BOSTON, Massachusetts — At long last, there appears to be an effective treatment for the pain related to oral mucositis experienced by patients head and neck cancer, according to a new phase 3 study.

An oral rinse containing the antidepressant doxepin significantly eased pain in patients with acute oral mucositis caused by radiation therapy, with or without chemotherapy, researchers reported here at the American Society for Radiation Oncology 54th Annual Meeting.

This makes doxepin a "new standard of care" for oral mucositis, lead study author Robert Miller, MD, from the Mayo Clinic in Rochester, Minnesota, told Medscape Medical News at a meeting press conference.

More study is needed to confirm the results, said Benjamin Movsas, MD, from the Henry Ford Hospital in Detroit, Michigan, who moderated the press conference. But it is an "exciting development" because "there is nothing out there for head and neck patients [with oral mucositis], said Dr. Movsas.

The Mayo Clinic now treats all cancer patients with oral mucositis with doxepin, Dr. Miller said.

The painful mouth sores seen with oral mucositis can be debilitating and can affect eating and drinking. The condition is the result of tissue damage caused by radiation therapy. A "very high percentage" of head and neck cancer patients treated with radiation will develop oral mucositis, said Dr. Miller.

Patients with oral mucositis are typically treated with narcotics, but nevertheless can experience "breakthrough pain," he explained. Doxepin is used for the treatment of this additional pain. Lidocaine is also used to treat oral mucositis, but is not well regarded by patients or clinicians, Dr. Miller explained.

Doxepin, which is a tricyclic antidepressant and no longer under patent, likely reduces pain by interacting locally with nerves in the oral cavity, he added.

Study Details

In this study, patients who reported a pain score of 4 or more on a 10-point scale participated in a 2-day protocol. On the first day, 155 patients received a single blinded dose of doxepin rinse (25 mg in 5 mL water) or placebo; on the second day, patients crossed over to the opposite group.

Compared with placebo, doxepin significantly decreased pain (P = .0003), which was measured by the area under the curve (AUC) on the pain scale over a 4-hour period after the administration of the rinse. Patients filled out a pain questionnaire and recorded pain levels at baseline and 6 other time intervals. The pain reduction peaked at the 30-minute mark for doxepin.

Overall, patients who received doxepin reported a larger reduction in pain than those who received placebo (AUC score, –9.1 vs –4.7), according to the study abstract. The results were similar for the crossover data (AUC score, –7.9 vs –5.6).

After the study was completed, 64% of patients elected to continue doxepin.

Although doxepin was well tolerated, patients reported 3 outstanding adverse effects that were more common with doxepin than with placebo: increased stinging/burning (mean pain score, 3.7 vs 1.1), unpleasant taste (mean unpleasant taste at 5 minutes, 2.9 vs 1.6), and greater drowsiness (mean drowsiness score, 3.9 vs 2.8), according to the study abstract.

Some previous research suggested that doxepin had a role to play in this setting. In a pilot study, doxepin reduced oral mucositis caused by radiation when used as a mouth rinse (J Pain Symptom Manage. 2007;33:111-114).

The study was conducted through the Alliance for Clinical Trials in Oncology (NCCTG/CALGB/ACOSOG).

American Society for Radiation Oncology (ASTRO) 54th Annual Meeting: Abstract LBA2 N09C6. October 29, 2012.