Pilot Trial of "Chemo-Switch" Regimen to Treat Advanced Melanoma

Inclusion Criteria:

* Must have histologically or cytologically confirmed melanoma that is locally advanced or metastatic. Cutaneous, mucosal, ocular, and unknown primary melanoma are all eligible.
* Must have measurable disease, defined by RECIST as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20mm with conventional techniques or \>10mm with spiral CT scan.
* May have received prior radiation therapy to one or more non-index lesions (prior radiation to an index lesion is allowable only if progression of the irradiated lesion is demonstrated, with progression defined as an increase of 20% or more in the largest diameter) and/or one prior vaccine therapy for metastatic disease. Prior adjuvant therapy with IFN alpha-2b, vaccine, and/or granulocyte-macrophage colony-stimulating factor (GM-CSF) is permitted. At least 4 weks must have elapsed since the completion of any prior therapy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Patients must have normal organ and marrow function as defined below:
* leukocytes \>3,000/uL (microliters)
* absolute neutrophil count \>1,500/uL
* platelets \>100,000/uL
* total bilirubin \<2.0mg/dL
* AST (Aspartate transaminase)(SGOT)/ALT (Alanine transaminase)(SGPT) \<2.5 X institutional upper limit of normal
* creatinine \<1.8mg/dL
* If \>50 years of age with one or more cardiac risk factors, must demonstrate normal exercise stress test, stress thallium test, or comparable cardiac ischemia evaluation.
* Must be at least 2 weeks out from major surgery and be free of any active infection requiring antibiotics.
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Women must demonstrate a negative pregnancy test prior to initiation of protocol therapy.
* Ability to understand and the willingness to sign a written informed consent form.

Exclusion Criteria:

* Prior chemotherapy, cytokine therapy (including IL-2 or IFN alpha), or antibody therapy for metastatic disease. Prior vaccine therapy is permitted.
* May not be currently receiving any other antineoplastic treatments, including chemotherapy, biologic response modifiers, radiation, vaccine, or investigational agents.
* History of brain metastases.
* Autoimmune disorders that could result in life-threatening complications in the setting of IFN alpha and IL-2 treatment.
* History of sensitivity to E. coli-derived products.
* Concurrent use of corticosteroids or any medical condition likely to require the use of systemic corticosteroids.
* A seizure disorder currently requiring anti-epileptic medication.
* Uncontrolled intercurrent illness including, but not limited to, hypertension, active infection requiring antibiotic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Evidence of bleeding diathesis.
* Currently on therapeutic anticoagulation. Prophylactic anticoagulation (such as low-dose warfarin) of venous or arterial access devices is allowed provided the PT, PTT (Partial Thromboplastin Time), and international normalized ratio (INR) are normal.