Leenstra, J.L., Miller, R.C., Qin, R., Martenson, J.A., Dornfeld, K.J., Bearden, J.D., ... Loprinzi, C.L. (2014). Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: A phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). Journal of Clinical Oncology, 32, 1571–1577.
To test the efficacy of doxepin hydrochloride in reducing radiotherapy-induced oral mucositis pain
Arm 1: Doxepin oral rinse 10 mg/ml x 2.5 ml = 25 mg diluted with sterile or distilled water for a total of 5 ml. Arm 2: Placebo rinse prepared in similar manner with flavored syrup added. Study dose was prepared by unblinded nurse or pharmacist. Blinded personnel administered the rinse. On day 1, the patients swished for one minute, gargled, and spit. On day 2, patients received the opposite rinse. Patients completed symptom questionnaires at set time intervals during the hour following administration and then again at home at two and four hours. No analgesics or oral rinses were allowed 60 minutes prior to and following the study doses. Patients returned the next time their oral pain was ≥ 4/10 and received their second study dose, after which they were unblinded and given the option to continue use of doxepin rinses prn. Patient-reported questionnaires with numerical pain analog scale (0–10) done at BL, 5, 15, 30, 60, 120, and 240 minutes after the rinse on days 1 and 2 to measure pain, taste, stinging or burning, and drowsiness.
Randomized, double-blind, placebo-controlled, phase III trial with crossover phase followed by continued use of active agent
Primary outcome: AUC for mean mouth and throat pain reduction was greater for doxepin compared with placebo (–4.4 difference p < .001). Crossover data revealed similar findings with –2.3 difference p < .001.
Largest placebo-controlled trial to date for oral mucositis pain with positive results
This is a promising option for mucositis pain although there are concerns about how the solution will be made, the cost, the ease of use, the side effects, and adherence to the rinse. Additional questions exist concerning whether or not this data can also be applied to patients receiving chemotherapy or those who have cancers other than head and neck cancer.