Inclusion Criteria:

• Patient has histologically proven squamous cell carcinoma of the head and neck which is biopsy accessible and is not considered curable by standard measures.
• Patient has a Karnofsky performance status >/= 70%
• Patient has adequate bone marrow function: *WBC >/= 3,000 cells/mm^3, *ANC >/= 1,500 cells/mm^3, *platelet count >/= 100,000 cells/mm^3, *Hgb >/= 9.0 g/dL.
• Patient has adequate liver function: *total bilirubin level </= 2.0 mg/dL, *albumin >/= 2.5 g/dL.
• Transaminases (SGOT and/or SGPT) may be up to 2.5 x ULN if alkaline phosphatase is </= ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are </= ULN.
• Patient has adequate renal function: a serum creatinine < 2 mg/dl
• Patient has signed a written informed consent.
• Patient has received no more than 2 prior chemotherapeutic regimens for recurrent or metastatic disease. Prior biologic therapy is not included.

Exclusion Criteria:

• Patient has received 3 or more prior chemotherapeutic regimens for recurrent/metastatic disease.
• No biopsy accessible tissue.
• Patient has received radiation therapy within the past 6 months.
• Prior radiation to the biopsy site.
• Patient has signs or symptoms of acute infection requiring systemic therapy.
• Patient exhibits confusion, disorientation, or has a history of major psychiatric illness which may impair patient’s understanding of the informed consent.
• Patient has grade 3 or 4 neurotoxicity from previous anticancer treatment or significant neuropathy from any cause.
• Patient requires total parenteral nutrition with lipids.
• Surgery is anticipated to leave patient unable to swallow the SCH66336 or 4-HPR daily.
• Patient has a history of uncontrolled heart disease (including arrhythmia, angina, congestive heart failure, or any heart condition that cannot be controlled with regular ongoing medication)
• Because of the known teratogenic effect of retinoids, pregnant women and women who are currently breast-feeding may not participate in this study. All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.
• Serious infection or other intercurrent illness requiring immediate therapy.
• Inability to swallow oral medications, or other medical or social factors interfering with compliance.
• Patients may not take high dose synthetic or natural Vitamin A derivatives (>10,000 IU per day). Patients may not be taking high-dose vitamin A within 30 days of study entry.
• Patients should not take any anti-oxidants such as Vitamin E or Vitamin C
• Patients with pre-existing retinopathy