Pemetrexed and Gemcitabine in Patients With Advanced Head and Neck Cancer

Inclusion Criteria: * Diagnosis of squamous cell cancer of the head and neck - unresectable or metastatic. Must have measurable disease by RECIST. * Karnofsky performance status greater than or equal to 60% * Up to one prior systemic chemotherapy, immunotherapy allowed in the advanced or metastatic setting. This does not include prior chemotherapy, immunotherapy used with radiotherapy (ie concurrent with radiation therapy or as and induction regimen pror to definitive radiation therapy). * At least 4 weeks from prior radiation or chemotherapy, must have recovered from all acute effects of treatment. * Adequate organ and marrow function * Negative pregnancy test. Agree to use birth control during and for 3 months after last dose of study drug. * At least 18 years of age. * Sign an informed consent and HIPAA consent. * Must be able to take and absorb enteral medication. Exclusion Criteria: * Serious concomitant systemic disorder that would compromise safety or ability to complete study. * Prior treatment with gemcitabine or pemetrexed within the previous year, unless used concurrently with radiation therapy. * Pregnancy or breastfeeding. * Symptomatic or uncontrolled brain mets. If treated, must be off steroids for at least 2 weeks. * Inability or unwilling to take folic acid, vitamin B12, or dexamethasone. * Treatment within last 30 days with a drug that has not received regulatory approval for any indication. * Inability to interrupt and NSAID or salicylate with a long half-life (piroxicam or nabumetone) for a 5 day period. * Presence of clinically relevant third space fluid that cannot be controlled by drainage or other procedure prior to study entry. * Active, concurrent, invasive malignancy requiring ongoing treatment. * Corticosteroids impermissible unless for adrenal failure, septic shock or as temporizing measure for symptomatic pain, breathing, or rash.