doxepin hydrochloride in treating oral mucositis pain in patients with head and neck cancer undergoing radiation therapy with or without chemotherapy

Conditions: Head and Neck Cancer; Mucositis; Oral Complications of Radiation Therapy; Pain

Summary: rationale: doxepin hydrochloride may be an effective treatment for oral mucositis pain in patients undergoing radiation therapy with or without chemotherapy. purpose: this randomized phase iii trial is studying doxepin hydrochloride to see how well it works compared to placebo in treating oral mucositis pain in patients with head and neck cancer undergoing radiation therapy with or without chemotherapy.

outline: this is a multicenter study. patients are stratified according to gender, concurrent radiosensitizing chemotherapy (yes vs no), and age (\< 60 years vs ≥ 60 years). patients are randomized to 1 of 2 treatment arms. * arm i: patients receive doxepin hydrochloride oral rinse (swish, gargle, and spit)\* over 1 minute on day 1. patients may crossover to arm ii on day 2. * arm ii: patients receive placebo oral rinse (swish, gargle, and spit)\* over 1 minute on day 1. patients may crossover to arm i on day 2. the primary and secondary objectives are detailed below. primary objective: determine whether doxepin oral rinse is effective in reducing om-related pain in patients undergoing rt to the oral cavity, as measured by a patient-reported questionnaire at 5,15, 30, 60, 120 and 240 minutes secondary objectives: 1. assess the adverse event profile of doxepin rinse using a patient-reported questionnaire at 5, 15, 30, 60, 120 and 240 minutes for domains of unpleasant taste, burning or stinging discomfort, and drowsiness. 2. compare the incidence of using alternative analgesics before 4 hours, between the doxepin oral rinse and placebo arms. 3. assess patient preference for continued therapy with oral rinse after initial test rinse or after the cross-over phase. note: \* patients are instructed to avoid taking medications for mucositis pain 60 minutes before and after study medication. after completing study therapy, patients have the option to receive doxepin hydrochloride oral rinse every 4 hours as needed during radiotherapy. patients complete questionnaires at baseline, and at 5, 15, 30, 60, 120, and 240 minutes after study medication. patients who choose to continue doxepin hydrochloride oral rinse also complete weekly questionnaires.

Eligibility criteria:
inclusion criteria: 1. ≥ 18 years of age 2. histologic proof of malignancy currently undergoing a course of rt (with or without chemotherapy) to a dose of ≥ 5000 cgy using 1.60 to 2.20 gy per fraction. note: at least one third of the oral cavity mucosa must be included in the radiation therapy fields. 3. ≥ 4 oral pain felt to be related to mucositis for which the patient wants relief as measured by the numeric measure of oral pain. note: an oral exam confirming the presence of mucositis should be performed by the enrolling clinician in addition to patient feedback. 4. ability to complete questionnaire(s) independently or with assistance 5. ecog performance status 0, 1 or 2. 6. provide informed written consent. 7. willingness to return to enrolling institution for follow-up. exclusion criteria: 1. known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation 2. use of a tricyclic antidepressant or monoamine oxidase inhibitor within the 2 weeks prior to registration 3. current untreated or unresolved oral candidiasis or oral hsv infection 4. current untreated narrow angle glaucoma 5. current untreated urinary retention ≤ 6 weeks prior to registration 6. co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens 7. any of the following because this study involves a study agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: * pregnant women * nursing women * men or women of childbearing potential who are unwilling to employ adequate contraception

Keywords: oral complications of radiation therapy mucositis pain stage i squamous cell carcinoma of the paranasal sinus and nasal cavity recurrent squamous cell carcinoma of the hypopharynx squamous cell carcinoma of the hypopharynx recurrent squamous cell carcinoma of the larynx recurrent verrucous carcinoma of the larynx squamous cell carcinoma of the larynx verrucous carcinoma of the larynx recurrent adenoid cystic carcinoma of the oral cavity recurrent mucoepidermoid carcinoma of the oral cavity recurrent verrucous carcinoma of the oral cavity adenoid cystic carcinoma of the oral cavity mucoepidermoid carcinoma of the oral cavity verrucous carcinoma of the oral cavity squamous cell carcinoma of the lip and oral cavity recurrent basal cell carcinoma of the lip recurrent squamous cell carcinoma of the lip and oral cavity basal cell carcinoma of the lip metastatic squamous neck cancer with occult primary squamous cell carcinoma recurrent metastatic squamous neck cancer with occult primary untreated metastatic squamous neck cancer with occult primary recurrent lymphoepithelioma of the nasopharynx recurrent squamous cell carcinoma of the nasopharynx lymphoepithelioma of the nasopharynx squamous cell carcinoma of the nasopharynx recurrent lymphoepithelioma of the oropharynx recurrent squamous cell carcinoma of the oropharynx lymphoepithelioma of the oropharynx squamous cell carcinoma of the oropharynx recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity recurrent inverted papilloma of the paranasal sinus and nasal cavity recurrent midline lethal granuloma of the paranasal sinus and nasal cavity recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity esthesioneuroblastoma of the paranasal sinus and nasal cavity inverted papilloma of the paranasal sinus and nasal cavity midline lethal granuloma of the paranasal sinus and nasal cavity squamous cell carcinoma of the paranasal sinus and nasal cavity high-grade salivary gland mucoepidermoid carcinoma low-grade salivary gland mucoepidermoid carcinoma recurrent salivary gland cancer salivary gland acinic cell tumor salivary gland adenocarcinoma salivary gland adenoid cystic carcinoma salivary gland anaplastic carcinoma salivary gland malignant mixed cell type tumor salivary gland poorly differentiated carcinoma salivary gland squamous cell carcinoma salivary gland cancer tongue cancer