Combination Chemotherapy Plus Biological Therapy in Treating Patients With Metastatic Melanoma

OBJECTIVES:

• Determine the toxicity of cisplatin and dacarbazine followed by sargramostim (GM-CSF), interferon alfa, and interleukin-2 in patients with metastatic melanoma.
• Determine the objective response rate, relapse free survival, and overall survival of these patients on this regimen.

OUTLINE: Patients receive cisplatin IV over 1 hour and dacarbazine IV over 30-60 minutes sequentially on day 1, followed by sargramostim (GM-CSF) subcutaneously (SC) on days 2-7, interleukin-2 SC on days 8-14, and interferon alfa SC on days 8, 10, 12, and 14. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression, and then every 8-12 weeks thereafter.

PROJECTED ACCRUAL: A total of 15-45 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic melanoma

• Stage III with intransit metastases
• Stage IV
• No uncontrolled brain metastases by CT scan
• No clinically significant ascites or pleural effusions

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 10 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.5 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT no greater than 4 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 70 mL/min

Cardiovascular:

• No clinically significant cardiac disease on EKG, echocardiogram, or MUGA scan

Pulmonary:

• No clinically significant pulmonary disease on chest x-ray

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant thyroid dysfunction
• No concurrent severe infection
• No other medical or psychiatric condition that would interfere with compliance
• No second malignancy within the past 5 years, except:

• Localized nonmelanomatous skin cancer
• Carcinoma in situ of the cervix
• Grade 1 Ta bladder cancer
• Suspected hearing deficits must undergo audiologic testing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No more than one prior immunotherapy regimen
• At least 4 weeks since prior immunotherapy
• Adjuvant interferon alfa before relapse allowed

Chemotherapy:

• No more than one prior chemotherapy regimen
• At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas)
• No concurrent cyclophosphamide
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent corticosteroids or cyclosporine A

Radiotherapy:

• At least 2 weeks since prior radiotherapy

Surgery:

• At least 3 weeks since major surgery

Other:

• No concurrent immunosuppressive drugs
• No other concurrent investigational antineoplastic drugs
• Concurrent thyroid replacement therapy allowed