Inclusion Criteria:

• Patients must have histologically confirmed, surgically nonresectable Stage III or IV metastatic cutaneous, mucosal, or choroidal melanoma, and not be eligible for a treatment protocol of a higher priority.
• Patients must have secondary tumor involvement of the liver confirmed by CT scan and a bilirubin level of 1.6-3.0 mg/dL (National Cancer Institute, Common Terminology Criteria for Adverse Events Grade 2) (MD Anderson Cancer Center normal range is 0-1.0 mg/dL).
• Patients must have bidimensionally measurable disease.
• Patients with nonchoroidal melanoma must have received prior chemotherapy for metastatic disease with cytotoxic or biological drugs. Patients with choroidal melanoma may or may not have received prior chemotherapy for metastatic disease with cytotoxic or biological drugs.
• Patients must have a Performance Status of 0, 1, 2, or 3 (Zubrod Scale).
• Patients must have recovered from the adverse effects of prior chemotherapy (including cytotoxic agents and biological response modifiers), and/or irradiation therapy.
• Patients must have an absolute neutrophil count ≥1.0 x 10*9/L and a platelet count of ≥100 x 10*9/L.
• Patients must have adequate renal function demonstrated by a creatinine level of ≤2.0 mg/dL.
• Patients must have a life expectancy of >8 weeks.
• Patients must provide a signed informed consent document indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.

Exclusion Criteria:

• Patients treated with radiotherapy, chemotherapy, immunotherapy, vaccine treatment and/or alternative anticancer treatments (including investigational drugs) within 3 weeks prior to study enrollment.
• Patients treated with hepatic chemo-embolization within 4 weeks prior to study enrollment.
• Patients with severe hepatic impairment demonstrated by plasma ammonia levels >105 mMol/L or serum albumin <2.0 g/dL or serum bilirubin >3.0 mg/dL.
• Patients with serious intercurrent illness.
• Patients who have had major surgery within 4 weeks of enrollment.
• Patients with advanced symptomatic central nervous system (CNS) involvement by melanoma and those on phenytoin or requiring steroids for brain metastases, spinal cord compression, or meningeal "carcinomatosis".Patients with asymptomatic and stable metastatic CNS disease can be enrolled.
• Patients receiving treatment with phenytoin and/or corticosteroids within 1 week of enrollment. Patients must remain off of these medications for the duration of the treatment phase of the study.
• Patients with a history of neurological disorders unrelated to chemotherapy (including familial neurological diseases and acquired demyelinating disorders).
• Patients with Grade 3 or greater sensory, motor or autonomic neuropathy at screening from any cause.
• Patients receiving treatment with drugs known to inhibit or induce hepatic drug metabolism by cytochrome P450-3A4 isoenzymes and/or P-glycoprotein within 1 week of study enrollment. Patients must remain off of these drugs until the collection of the Cycle 4 pretreatment PK sample.
• Patients with past or current history of liver parenchymal or hepatobiliary disease unrelated to cancer (including but not limited to conditions such as liver cirrhosis, acute/chronic hepatitis, ascending cholangitis, etc).
• Patients who are pregnant or lactating. Females of childbearing potential must have a negative urine or blood pregnancy test at screening. Both men and women must be practicing an adequate method of birth control for the duration of the study. Acceptable methods of birth control include use of an intrauterine device (IUD), oral contraceptive pills, implanted, transdermal, or injected contraceptives, barrier methods with spermicide, and abstinence.
• Patients who are unable to return for follow up re-evaluation and assessment of response to VSLI.