A Phase I Trial of Normothermic Isolated Limb Infusion (ILI) With Melphalan Plus Buthionine Sulfoximine (BSO) in Patients With Locally Advanced Malignant Melanoma

DISEASE CHARACTERISTICS:

• Histologically proven primary or recurrent in-transit melanoma of the extremity
• Stage IIIB or IIIC disease, as determined by whole body imaging with a CT scan of the chest, abdomen, and pelvis AND PET scan within the past 4 weeks
• Patients with stage IIIC disease must have undergone removal of regional lymph nodes
• Patients with indeterminate staging must be reviewed by the study chairs prior to study registration
• Previously treated with melphalan-based regional therapy and had persistent disease at 3 months OR achieved a complete response but disease recurred within 6 months
• Disease to be treated by regional therapy must be distal to the planned site of tourniquet placement
• Bidimensionally measurable disease by caliper or a radiological method as defined by the RECIST criteria modified for cutaneous lesions
• Photo documentation required
• Patients with a single lesion must have archived tumor tissue available for study analysis
• No history of tumors with clinically significant evidence of active bleeding (e.g., gross hemoptysis, hematemesis, hematuria, melena, or bleeding superficial tumor) within the past 12 weeks
• No stage IV disease
• No cerebral metastases

PATIENT CHARACTERISTICS:

• ECOG/Zubrod performance status 0-1
• Serum creatinine ≤ 1.5 mg/dL
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Bilirubin normal
• AST and ALT ≤ 2.5 times normal
• Must have a palpable femoral/axillary pulse in the affected extremity
• No uncontrolled seizures or clinically significant CNS disorders
• No psychiatric condition or diminished capacity that could preclude study compliance or giving informed consent
• No history of allergic reactions and/or hypersensitivity to melphalan
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of other malignancies except adequately treated basal cell or squamous cell carcinoma of the skin; curatively treated carcinoma in situ of the uterine cervix, prostate cancer, or superficial bladder cancer; or other curatively treated solid tumors with no evidence of disease for ≥ 5 years
• No stroke or other major tissue injury within the past 4 weeks
• No other uncontrolled serious chronic disease or condition that, in the investigator's opinion, could preclude study compliance or follow-up

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• More than 4 weeks since prior major surgery
• Wound healing adequate since last major surgery
• More than 4 weeks since prior antineoplastic therapy, radiotherapy, or any other investigational drug
• More than 7 days since prior antimicrobial agents (i.e., antibiotic, antifungal, or antiviral agents) for active infection or infectious symptoms
• No drugs that are known to cause enhanced glutathione depletion (e.g., acetaminophen) for 7 days before, during, and for 7 days after buthionine sulfoximine (BSO) administration
• No cephalosporin antibiotics for 7 days before, during, and for 7 days after BSO administration