Phase II Trial of Erlotinib, Prior to Surgery or Radiation in Patients With Squamous Cell Cancers (SCC) of the Skin

Inclusion Criteria:

1. Within 12 weeks prior to study entry, patient must have histologically or cytologically confirmed cutaneous squamous cell carcinoma (CSCC) that is either locally advanced or recurrent, and no evidence of distant metastases. If the biopsy was collected outside of MD Anderson Cancer Center (MDACC), the MDACC Pathology Department must assess and confirm the SCC diagnosis.
2. Patient is eligible with previous surgical intervention if they have residual or recurrent disease, it is greater than 6 weeks since surgery and they have fully recovered from the surgery.
3. Patient must have measurable disease.
4. Tumor must be at least 2 centimeters in size as measured by the treating physician(s) or PI, or have histological or cytological verification of muscle, bone, lymph node metastasis, or perineural involvement,.
5. Surgical resection or radiation must be planned as part of the treatment strategy for the CSCC.
6. At least 18 years of age.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
8. Must have adequate organ and marrow function as follows:(a) leukocytes \>/= 3,000/mm\^3 (b) absolute neutrophil count \>/= 1,500/mm\^3 (c) platelets \>/= 75,000/mm\^3 (d) hemoglobin \>/= 8g/dL (e) total bilirubin \</= 2 X institutional upper limit of normal (ULN) (f) AST(SGOT)/ALT(SGPT) \</= 2.5 X ULN if alkaline phosphatase is normal, or alkaline phosphatase \</= 4 x ULN if transaminases are normal (g) Creatinine \</= 2.0 x ULN or creatinine clearance \>/= 60 mL/min/1.73 m\^2
9. Must be able to take intact tablets by mouth, or be able to take tablets dissolved in water by mouth or by a percutaneous gastrostomy tube.
10. Patients - both males and females - with reproductive potential (includes women who are menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Birth control should continue for 4 weeks after discontinuation of erlotinib therapy. Women of childbearing potential must provide a negative pregnancy test (serum betaHCG) within within 72 hours prior to first receiving protocol therapy.
11. Must have ability to understand and the willingness to sign a written Informed Consent Document (ICD). In the event that non-English speaking participants are eligible for this study, a short form (if applicable) or an ICD in their language will be utilized and completed in accordance with the MDACC "Policy For Consenting Non-English Speaking Participants."
12. Must be willing to receive their definitive local therapy, that is surgery and / or radiation therapy, at M. D. Anderson Cancer Center.
13. Organ transplant patients are eligible as long as they do not have active signs of rejection and have adequate bone marrow function.

Exclusion Criteria:

1. Women who are pregnant, breastfeeding, or have child-bearing potential \& are unwilling/unable to use an acceptable method of contraception for the entire study period \& for at least 4 weeks after cessation of the study drugs. If the pregnancy test is positive, the patient must not receive erlotinib, \& must not be enrolled on the study. Erlotinib is a signal transduction inhibitor agent w/ the potential for teratogenic or abortifacient effects.
2. -continued from Exclusion #1- If the pregnancy test is positive, the patient must not receive erlotinib, and must not be enrolled on the study. Erlotinib is a signal transduction inhibitor agent with the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with erlotinib, breastfeeding should be discontinued if the mother is treated with erlotinib.
3. Patient with distant metastatic disease.
4. Patient who has had previous radiotherapy to the site of the skin cancer being treated on this protocol.
5. Patient currently receiving any other anticancer or investigational agents at time of study enrollment.
6. Patient has received prior EGFR inhibitor therapy.
7. Patient with a history of an invasive malignancy (other than the one treated in this study) or lymphoproliferative disorder within the past 5 years. Patients with a history of adequately treated non-melanoma skin cancer, ductal carcinoma in situ of the breast or carcinoma in situ of the cervix are allowed.
8. Patient with history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib.
9. Patient is unwilling or unable to discontinue prohibited concomitant therapies.
10. In the opinion of the investigator, patient with any condition that is unstable or could jeopardize the safety of the patient or could limit compliance with the study's requirements. These include, but are not limited to, ongoing or active infection requiring parenteral antibiotics at time of study registration, psychiatric illness that would limit compliance with study requirements or symptomatic congestive heart failure (NYHA class II or greater), unstable angina pectoris or cardiac arrhythmia requiring maintenance medication.
11. Patient with a history of pulmonary fibrosis (other than in a radiated field) or chronic liver disease.
12. Patients with active gastrointestinal disease or a disorder that alters gastrointestinal motility or absorption; for example, a significant surgical resection of the stomach or small bowel, uncontrolled inflammatory bowel disease or uncontrolled chronic diarrhea.