Azacitidine and Cisplatin for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria: * Patients must have histologically proven SCCHN that is either metastatic or has persisted or recurred following definitive surgery and/or radiation therapy, and is not amenable to salvage surgical resection. * Patients may have received previous chemotherapy and/or biological treatment (such as cetuximab) for the recurrent or metastatic disease. Prior treatment must have been completed at least 28 days (42 days for nitrosoureas or mitomycin C) prior to entering the study and all toxicities must have been resolved. * Prior radiation must have been completed at least 28 days before entry into the study and all toxicities must have been resolved (no more than 3000 cGy to fields including substantial marrow). * Surgery must have been completed at least 28 days before entry into the study and all complications/adverse events must have been resolved. * Patients must have at least one lesion amenable to serial biopsy. * Age greater than 18 years. * ECOG performance status less than 2 (Karnofsky greater than 60%). * Life expectancy of greater than 3 months. * Patients must have normal organ and marrow function * Patients must not be planning to receive any other concurrent therapy (ie, radiation, chemotherapy, immunotherapy, biological therapy or gene therapy) for SCCHN while they are on this study. * Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment. Exclusion Criteria: * Patients must not be planning to receive any other concurrent therapy (ie, radiation, chemotherapy, immunotherapy, biological therapy, investigational agents or gene therapy) for SCCHN while they are on this study. * Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine, cisplatin and mannitol or other agents used in study. * Pregnant or nursing women may not participate in this trial because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients known to be HIV-positive are not eligible because of the potential to confound this study's endpoints. * No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for five years.