The proposed study is a first-in-human pilot of a novel anti-cancer strategy: Metnase inhibition to potentiate DNA damaging chemotherapy. The investigators will conduct serial tumor biopsies in subjects with HNSCC at three timepoints: baseline, after cisplatin, and after cisplatin-raltegravir. The investigators will investigate immunohistochemical expression changes of γH2AX, Chk2, and Annexin V, three biomarkers of DNA damage and apoptosis. The study is designed to identify an intermediate signal of the potentiation of cisplatin chemotherapy by raltegravir in HNSCC, which will justify a future phase I/II study.

Inclusion Criteria:

• Histologic or cytologic diagnosis of squamous cell carcinoma of the head and neck. All primary sites are eligible, including keratinizing nasopharyngeal carcinoma (WHO grade 1 or 2) and carcinoma of unknown primary.
• Either the primary site or a metastatic locoregional tumor deposit (eg. lymph node, parotid gland, subcutaneous nodule) must be amenable to repeat, in-office biopsy by a head and neck surgeon.
• The patient must be considered an appropriate candidate for cisplatin chemotherapy by a medical oncologist. Acceptable indications include induction chemotherapy prior to surgery or radiation for localized disease, or palliative chemotherapy for advanced disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate bone marrow function, defined as an absolute peripheral granulocyte count of greater than 1,500 cells/mm3 and platelet count greater than 100,000/mm3 and absence of a regular red blood cell transfusion requirement.
• Adequate hepatic function with a total bilirubin less than 2 mg/dl; SGOT and SGPT less than 1.5 times the upper limit of normal; alkaline phosphatase less than 2.5 times the upper limit of normal.
• Creatinine clearance greater than or equal to 55 mL/min. Creatinine clearance will be estimated by the Cockraft-Gault formula, using actual body weight.
• Women of childbearing potential must have a negative pregnancy test.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment, and for at least 3 months thereafter.
• Age greater than 18.
• Able to provide written, informed consent.

Exclusion Criteria:

• No known brain metastases.
• Pregnant women or nursing mothers are not eligible for this trial.
• During the first two weekly cycles of cisplatin and raltegravir, patients may receive no other concurrent antineoplastic therapy, including chemotherapy, biologic agents or radiotherapy. For subsequent induction or palliative chemotherapy cycles, patients may receive combination cisplatin-docetaxel-raltegravir, on a three-week schedule as specified in this protocol.
• No severe medical problems, including unstable angina; myocardial infarction within the past 6 months; symptomatic congestive heart failure, NYHA grade II or higher; active infection requiring antibiotics.
• History of hypersensitivity reaction to cisplatin.
• Patient with known HIV disease.
• Any comorbid condition which would preclude full compliance with the protocol.
• Patient is less than 3 years free from another malignancy, except: a) if the other malignancy is non-melanomatous skin cancer or cervical carcinoma in situ or b) if the other primary malignancy is considered clinically insignificant and is requiring no active intervention.
• Peripheral neuropathy greater than or equal to grade 2.
• Ongoing treatment with rifampin, phenytoin, or phenobarbital.