Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy

Inclusion Criteria:

* Newly diagnosed stage III-IV HNSCC, pathologically confirmed (HNSCC from unknown primary sites are allowed)
* No evidence of distant metastasis
* No prior radiation therapy to the head and neck sites.
* Able to sign a study-specific informed consent form.
* Women of childbearing potential and men with partners capable of producing offspring must be willing to practice acceptable methods of birth control to prevent pregnancy.
* Left ventricular ejection fraction (LVEF) within the institutional normal range as measured by ECHO (If ECHO cannot be performed or if the Investigator feels that it is not conclusive to evaluate LVEF, then a MUGA scan should be performed).
* Having one of the following parameters that would preclude the use of concurrent CRT:

  * ECOG PS \> 2.
  * Creatinine \> 1.3 or calculate or measure creatinine clearance \< 60 ml/min.
  * AST or ALT \> 1.5 times normal limit but \< 3 times normal limit
  * Total bilirubin \> 1.5 mg/dL but \< 3mg/dL
  * History of hearing loss that would preclude cisplatin chemotherapy. These would include the existing need of a hearing aid or a \>= 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test.
  * Pre-existing peripheral neuropathy that would preclude cisplatin chemotherapy
  * Refuse or cannot tolerate chemotherapy
* Age 18 years or older

Exclusion Criteria:

* Known hypersensitivity to lapatinib or any of the excipients of this product (quinazolines).
* Uncontrolled angina, arrhythmia or congestive heart failure at the time of HNSCC diagnosis and treatment.
* History of myocardial infarction \< 6 months from study entry.
* Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
* Prior treatment with EGFR or Her2/Neu directed therapies.
* HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Lapatinib.
* Absolute neutrophil count \< 1500/uL