Inclusion Criteria:

- Pathologically confirmed head and neck malignancy

- All subjects requiring radiotherapy to the head and neck for a poor-prognosis
malignancy will be eligible.

- Two cohorts of subjects: no prior history of head and neck radiation, i.e.
non-irradiated and prior history of head and neck radiation, i.e. previously
irradiated.

- Subjects with recurrent head and neck cancer with no clinically measurable distant
disease as well as those subjects in whom distant disease was of low volume and local
and regional palliation is clinically warranted will be eligible.

- Subjects without prior treatment should have stage IV disease (see AJCC staging
system in Appendix 2, Protocol) or have an expected long-term survival of less than
10%.

- No prior treatment with systemic anti-EGFR inhibitors or Pemetrexed. Any number of
prior systemic therapies is allowed.

- Measurable or evaluable disease.

- ECOG performance status 0-2 .

- Age ³ 18 years.

- Subjects must have fully recovered from the effects of any prior surgery,
chemotherapy, or radiation therapy. A minimum time period of 4 weeks should elapse
between the completion of prior chemotherapy and enrollment in the study.

- ANC ³ 1500/µl, platelet count ³ 100,000/µl. Hemoglobin should be >8 g/dL.

- Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault
formula: Calculated Creatinine Clearance = (140-age) X actual body wt.(kg) 72 X serum
creatinine Multiply this number by 0.85 if the subject is female

- Total bilirubin within normal limits and AST/ALT less than 3 times the upper limit of
normal (less than 5 times the upper limit of normal in the presence of liver
metastases).

- Informed consent must be obtained from all subjects prior to beginning therapy.
Subjects should have the ability to understand and the willingness to sign a written
informed consent document.

- Subjects should be willing and able to take folic acid and vitamin B12
supplementation and should interrupt aspirin or other nonsteroidal anti-inflammatory
agents for a 5-day period (8-day period for long acting agents such as piroxicam),
see section 5.57

Exclusion criteria:

- Subjects with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection or psychiatric illness/social situations that would limit
compliance with study requirements, significant history of uncontrolled cardiac
disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial
infarction (within prior 3 months), uncontrolled congestive heart failure, and
cardiomyopathy with decreased ejection fraction.

- May not be receiving any other investigational agents.

- Pregnant women are excluded from this. Breastfeeding should be discontinued if the
mother is treated with chemotherapy. Prior to study enrollment, women of
childbearing potential (WOCBP) must be advised of the importance of avoiding
pregnancy during trial participation and the potential risk factors for an
unintentional pregnancy. In addition, men enrolled on this study should understand
the risks to any sexual partner of childbearing potential and should practice an
effective method of birth control. Subjects who are women of childbearing potential
and sexually active males must be willing to use effective contraception while on
study.

- All WOCBP should be instructed to contact the Investigator immediately if they
suspect they might be pregnant .

- HIV-positive subjects are excluded from the study.

- Prior grade 3 or 4 infusion or hypersensitivity reaction to a monoclonal antibody.

- For subjects who have baseline clinically significant pleural or peritoneal effusions
before initiation of protocol therapy, consideration should be given to draining the
effusion prior to starting therapy due the potential of increased toxicity with
Pemetrexed in that setting.