Inclusion Criteria:

• Histological confirmation of thoracic malignancies including non-small cell lung cancer (NSCLC), small lung cancer (SCLC), lymphoma, thymoma, thymic carcinoma, mesothelioma, sarcoma, and pulmonary or pleural-based metastases
• Planned RT (with or without chemotherapy) to a dose of ≥ 20 Gray (Gy) using 1.60 to 4.00 Gy per daily fraction; if radiation is given twice daily, a cumulative planned dose of ≥ 15 Gy using 1.25 to 2.75 Gy per fraction is required
• At least 5 cm of the esophagus must be planned to receive radiotherapy, with a minimum dose of at least 10 Gy
• ≥ 4 esophageal pain, either at rest or during swallowing, felt to be related to esophagitis for which the patient wants relief, as measured by asking the following question
  • "On a scale of 0 to 10 (0 = no pain; 10 = worst pain), what number best describes your chest pain* (right now) due to your radiation treatment?"
    • Radiation can cause inflammation in your esophagus which can feel like a chest pain, either at rest or during swallowing
• Able to swallow
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Direct bilirubin < 2.0 x upper limit of normal (ULN)
• Aspartate transaminase (AST) ≤ 4 x ULN
• Negative pregnancy test done ≤ 28 days prior to registration, for women of childbearing potential only
• Ability to complete questionnaire(s) by themselves or with assistance
• Provide informed written consent
• Willingness to complete evaluation and questionnaires per protocol at the participating institution for follow-up (during the active monitoring phase of the study)
• Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

• Known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation
• Histologic proof of and getting treatment for esophageal, stomach, spinal cord, thyroid, breast, and head and neck cancers and vertebral metastases
• Use of a tricyclic antidepressant or monoamine oxidase inhibitor within the 2 weeks prior to registration
• The presence or strong clinical suspicion of a tracheoesophageal fistula, or known esophageal invasion by cancer
• Current untreated or unresolved esophageal candidiasis or herpes simplex virus (HSV) infection
• Current untreated narrow angle glaucoma
• Current untreated urinary retention ≤ 6 weeks prior to registration
• 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
• Any of the following
  • Pregnant women
  • Nursing women