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