• Percentage of responders with response duration > 6 months [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the response rate and duration of response in patients with unresectable hepatic metastases secondary to ocular melanoma treated with isolated hepatic perfusion with melphalan followed by temozolomide.
• Determine the pattern of recurrence in patients treated with this regimen.
• Determine the disease-free and overall survival of patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.

OUTLINE: Patients who are otherwise eligible undergo exploration through a limited incision. Patients with peritoneal seeding or unresectable extrahepatic metastatic disease are removed from study. All other patients undergo isolated hepatic perfusion (IHP) and receive melphalan intra-arterially over 1 hour.

Within 8-12 weeks after IHP, patients are re-evaluated by MRI. Patients with stable or responding disease receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 8-12 weeks after IHP, every 3 months during temozolomide, and at all follow-up visits.

Patients are followed every 3 months for 2 years and then every 4 months thereafter.

PROJECTED ACCRUAL: A total of 9-40 patients will be accrued for this study

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed ocular melanoma

  • Metastatic disease confined to the liver
  • Limited sites of extrahepatic disease allowed, provided the dominant life-limiting disease is in the liver and the extrahepatic sites can be treated with local ablative measures (e.g., resection or external beam radiotherapy)
• Measurable disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Platelet count greater than 75,000/mm^3
• Hematocrit greater than 27%
• Absolute neutrophil count at least 1,500/mm^3

Hepatic

• Bilirubin less than 2.0 mg/dL
• PT no greater than 2 seconds above the upper limit of normal (ULN)
• AST and ALT no greater than 10 times ULN
• No biopsy proven cirrhosis
• No evidence of significant portal hypertension by history, endoscopy, or radiologic study

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular

• No history of congestive heart failure with LVEF less than 40%
• No history of veno-occlusive disease

Pulmonary

• No chronic obstructive pulmonary disease
• No other chronic pulmonary disease with pulmonary function tests less than 50% of predicted

Other

• Not pregnant or nursing
• Negative pregnancy test
• Weight greater than 30 kg
• No active systemic infection
• No prior hypersensitivity reaction to melphalan, dacarbazine, or temozolomide

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 28 days since prior biologic therapy for the malignancy

Chemotherapy

• More than 28 days since prior chemotherapy for the malignancy

Endocrine therapy

• Not specified

Radiotherapy

• More than 28 days since prior radiotherapy for the malignancy

Surgery

• Not specified

Other

• Recovered from all prior therapy
• No concurrent chronic anticoagulation therapy
• No concurrent immunosuppressive drugs