imageBoston—A large clinical trial has shown that a water-based rinse containing the tricyclic antidepressant doxepin reduces mucositis pain in patients with head and neck cancer who are undergoing radiotherapy.

Robert Miller, MD, a professor of radiation oncology at Mayo Clinic in Rochester, Minn., who presented the study at the annual meeting of the American Society for Radiation Oncology (abstract LBA2), said doxepin provides a new standard for treatment of radiotherapy-induced oral mucositis.

The Alliance for Clinical Trials in Oncology launched the N09C6 trial, a double-blind, Phase III randomized controlled trial, after a small study suggested doxepin—approved for depression/anxiety and moderate pruritus but used off-label for pain conditions—reduces mucositis pain in patients with cancer (J Pain Symptom Manage 2007;33:111-114).

The study enrolled 155 adults with head and neck cancer from 26 institutions. The patients were eligible if they had received radiation therapy in which at least 30% of the oral cavity was treated and had developed mucositis pain of at least a 4 on a scale of 0 to 10. Patients received a single dose of doxepin, 25 mg of the drug in 5 mL of water, or a placebo of water on day 1 of the study. On day 2, patients crossed over to receive the opposite agent. Roughly 80% of patients received concurrent chemotherapy, and baseline patient characteristics were balanced in the two arms.

Pain was assessed on a scale of 1 to 10 via a questionnaire that was completed at baseline and then at five, 10, 30, 60, 120 and 240 minutes post-baseline. The primary study end point was total pain reduction, as calculated by average patient-reported mouth and throat pain, measured over the four-hour period after drug administration on day 1. Doxepin was more effective at reducing pain (area under the curve reduction, –9.1 vs. –4.7; P=0.0003). On average, over time doxepin reduced a patient’s pain score by 2 points, whereas placebo reduced the score by 1 point.

Patients receiving doxepin reported a temporary burning and stinging, an unpleasant taste and a mild increase in drowsiness, but the agent was well tolerated. After the double-blind, crossover portion of the study, 64% of patients opted to continue using doxepin (P=0.002).

“There are many institutional recipes for head and neck cancer symptom treatment, but relatively limited rigorous clinical trial data,” commented Paul Harari, MD, the chairman of human oncology at the University of Wisconsin, in Madison. Before calling doxepin a new standard of care, he said further research was warranted. One goal for such investigations, he noted, should be to determine whether the transient 1-point reduction in pain score over placebo seen in the NO9C6 trial justifies the introduction of a new class of agent for these patients or whether a slight adjustment in pain medication or numbing rinse might achieve the same effect.

Dr. Miller reported that he is involved with Tekcapital’s scientific advisory board. Dr. Harari reported no relevant financial conflicts of interest.