Phase II Trial of Extended-Dosing Temozolomide in Patients With Melanoma

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.