Inclusion Criteria:

- Stage III (unresectable) or Stage IV melanoma from a cutaneous or an unknown primary.

- Histologic proof of melanoma reviewed and confirmed at MSKCC

- Measurable disease (RECIST criteria)

- No prior chemotherapy for melanoma. Prior interferon, interleukin-2 or vaccine
therapy are allowed.

- No other concurrent chemotherapy, immunotherapy, or radiotherapy

- Karnofsky performance status ≥ 60

- Adequate organ function defined as follows: ANC > 1500, Platelets > 100,000,
creatinine < 2, Alkaline Phosphatase, AST and total bilirubin < 1.5x upper limit of
normal. For patients with suspected Gilbert's syndrome bilirubin will not be a
requirement.

- Tumor tissue for MGMT promoter methylation analysis and/or IHC must be available. In
most cases, this will be unstained slides from previously-obtained paraffin-embedded
tumor material. If this is not available, patients must have an easily-accessable
tumor for biopsy (e.g. skin or lymph node).

Exclusion Criteria:

- History of CNS metastases unless brain metastases have been resected and the patient
has been free from CNS recurrence for 6 months.

- Uveal or mucosal melanoma primary

- Frequent vomiting or medical conditions that could interfere with oral medication
intake

- Serious infection requiring antibiotics, or nonmalignant medical illnesses that are
uncontrolled or whose control might be jeopardized by the complications of this
therapy.

- History of HIV infection even if on HAART

- Immunosuppressive drugs

- High dose vitamins and herbs

- Other on-going investigational therapy, concurrent chemotherapy, immunotherapy or
radiotherapy.