Evaluate Safety/Tolerability Intra-Arterial Temozolomide in Patients w/Extremity Melanoma by Isolated Limb Infusion

Inclusion Criteria:

1. Patient must have undergone a previous Melphalan based regional therapy for which they did not respond optimally and present with persistent, progressive, or recurrent disease.
2. Patient must be 18 years of age or older.
3. Patient must have an ECOG status of 0-1.
4. Patient must have histologically proven primary or recurrent extremity melanoma, stage IIIB, IIIC, or IV
5. Patients with Stage IIIC disease must either have had regional lymph nodes previously removed or will have them removed at the time of regional treatment.
6. Patients with Stage IV disease must have had all distant disease resected at least 30 days prior to regional treatment.
7. Disease to be treated by ILI must be distal to the planned site of tourniquet placement
8. Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the RECIST criteria.
9. Patient must have adequate bone marrow, liver and renal function
10. Patient must have a palpable femoral/radial pulse in the affected extremity.
11. Recovery from relevant toxicity prior to first study drug administration.
12. Patients must have a life expectancy of \> 6 months.
13. Ability to read and understand English and the ability to complete paper +/- electronic survey assessments.

Exclusion Criteria:

1. Cardiac disease: Congestive heart failure \> class II NYHA.
2. Known brain metastasis.
3. Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
4. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
5. Active clinically serious infection \> CTCAE Grade 2.
6. Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
7. Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of administration of TMZ
8. Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of administration of TMZ.
9. Serious non-healing wound, ulcer, or bone fracture.
10. Major surgery or significant traumatic injury within 30 days of ILI.
11. Evidence or history of bleeding diathesis or coagulopathy.
12. Antineoplastic therapy, radiotherapy, or any other investigational drug within 30 days prior to first study drug administration.
13. Patients with symptoms or signs of vascular insufficiency. Specifically, patients with any history of blood clots or lifestyle altering ischemic peripheral vascular disease will be excluded.
14. History of allergic reactions and/or hypersensitivity to TMZ.
15. Psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance.
16. Pregnant or nursing women are not eligible for this study. Patients of reproductive potential must agree to use an effective method of birth control when undergoing treatments with known or possible mutagenic or teratogenic effects. All female participants of child-bearing potential must have a negative serum pregnancy test within two weeks of patient registration. Please note: use of contraception, including surgical procedures such as vasectomy or tubal ligation DO NOT eliminate the need for administering pregnancy testing.
17. Current treatment, or treatment in the previous 24 months, for another non-melanoma malignancy.
18. Unable to return at the regular required intervals for reassessment, or study drug administration.
19. Patients with known heparin induced thrombocytopenia.