RATIONALE: Drugs used in chemotherapy such as melphalan and temozolomide use different ways
to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy drugs in
different ways may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of isolated hepatic (liver) perfusion
with melphalan followed by temozolomide in treating patients who have unresectable liver
metastases that has resulted from ocular (eye) melanoma.
- 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
- 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
- 18 and over
- ECOG 0-2
- Not specified
- Platelet count greater than 75,000/mm^3
- Hematocrit greater than 27%
- Absolute neutrophil count at least 1,500/mm^3
- 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
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
- No history of congestive heart failure with LVEF less than 40%
- No history of veno-occlusive disease
- No chronic obstructive pulmonary disease
- No other chronic pulmonary disease with pulmonary function tests less than 50% of
- 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:
- More than 28 days since prior biologic therapy for the malignancy
- More than 28 days since prior chemotherapy for the malignancy
- Not specified
- More than 28 days since prior radiotherapy for the malignancy
- Not specified
- Recovered from all prior therapy
- No concurrent chronic anticoagulation therapy
- No concurrent immunosuppressive drugs