Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy

You may be eligible if

• 1. Documentation of Disease: Histologic documentation of malignancy currently undergoing a course of RT (with or without chemotherapy) including the oral cavity and/or oropharyngeal area to a dose of at least 4500 cGy using more than 5 fractions (i.e., stereotactic body radiation therapy \[SBRT\] is not allowed).
• 2. Physical exam demonstrating evidence of radiotherapy-related mucositis in the visible oral cavity and/or oropharynx consistent with mucous membrane toxicity greater than 0 using the Acute Radiation Morbidity Scoring Criteria.
• 3. At least 4 (out of 10) patient-reported oral pain related to oral mucositis secondary to RT for which the patient seeks relief, as measured on the Oral Pain Assessment.
• Note: The pain score must be at least 4 at the time that the patient starts the first dose of study medication. The patient may be enrolled to the study if s/he, at times, has a pain score of at least 4, so long as initiation of study treatment begins when the pain score is at least 4.
• 4. Ability to complete questionnaire(s) by themselves or with assistance.
• 5. No known allergy to diphenhydramine, lidocaine, antacid (aluminum hydroxide, magnesium hydroxide, and simethicone), doxepin, tricyclic antidepressants, or any known component of the drug formulation in the testing arms.
• 6. No use of any anti-arrhythmic medication (except for beta-blockers) including lidocaine, linezolid, ipratropium, or medications with high anti-cholinergic potency (including neostigmine, a tricyclic antidepressant or a monoamine oxidase inhibitor) within 2 weeks prior to registration.
• 7. No current diagnosed untreated or unresolved oral candidiasis or oral HSV infection.
• 8. No history of untreated narrow angle glaucoma within 6 weeks prior to registration.
• 9. No untreated urinary retention within 6 weeks prior to registration.
• 10. No current use of glutamine or sucralfate powders at the time of registration (no washout required).
• 11. No cryotherapy for prophylactic mucosal protection within 6 weeks prior to registration.
• 12. Not pregnant, because patients eligible for this study will be receiving radiotherapy, which has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 28 days prior to registration is required.
• 13. Age ≥ 18 years
• 14. ECOG Performance Status 0, 1, or 2