Phase II Trial of Pemetrexed-Based Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Previously Irradiated Head and Neck Cancer Patients

Inclusion Criteria: * All previously irradiated patients with recurrent head and neck cancer with no clinically measurable distant disease or those patients in whom distant disease was of low volume and local and regional palliation is clinically warranted. Low volume metastatic disease is defined as asymptomatic or minimally symptomatic disease that, according to physician judgment and without therapy for locoregionally recurrent disease, is unlikely to effect the subject's quality or quantity of life. * Histologic or cytological documentation of recurrent head and neck cancer requiring regional therapy. * Prior radiation therapy completed \> 4 months before to study entry, if patients have recovered from all side effects grade 1. * Predominance of disease that is amenable to radiotherapy. * Measurable disease prior to induction chemotherapy. * Age \>18 years * Life expectancy of greater than 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky \> 70%). * Patients must have normal organ and marrow function as defined below: Leukocytes \>3,000/ul Absolute neutrophil count \>1,500/ul Platelets \>100,000/ul Total bilirubin \< 1.5X institutional upper limit of normal AST (SGOT)/ALT(SGPT) \< 2.5 X institutional upper limit of normal Creatinine Clearance (CrCl) \> 45 mL/min The standard Cockcroft and Gault formula (based on actual weight) or the measured glomerular filtration rate (GFR) using the appropriate radiolabeled method (51-CrEDTA or Tc99m-DTPA) must be used to calculate CrCl for enrollment or dosing. The same method used at baseline should be used throughout the study. Insufficient numbers of patients have been studied with creatinine clearance \<45 mL/min to give a dose recommendation. Therefore, pemetrexed should not be administered to patients whose creatinine clearance is \<45 mL/min. Although ibuprofen and other non-steroidal inflammatory drugs (NSAID) can be administered with pemetrexed in patients with normal renal function (creatinine clearance 80 mL/min), caution should be used when administering NSAID concurrently with pemetrexed to patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min). Patients with mild to moderate renal insufficiency should avoid taking NSAID with short elimination half lives (e.g. ibuprofen) for a period of 2 days before, the day of, and 2 days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAID with longer half lives, all patients taking these NSAID should interrupt dosing for at least 5 days before, the day of, and 2 days following pemetrexed administration. If concomitant administration of an NSAID is necessary, patients should be monitored closely for toxicity, especially myelosuppression, renal, and gastrointestinal toxicity. * The presence of a significant infection or another severe complicating medical illness may constitute a contraindication to entrance on this protocol. * Pregnancy is an absolute contraindication for this treatment protocol. * Ability to understand and the willingness to sign a written informed consent document * Ability to swallow vitamins and dexamethasone or willingness to use a feeding tube to ingest these agents Exclusion Criteria: Previously untreated patients are not eligible Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may not be receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical composition agents used in the study. 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.