Temozolomide and Interferon Alfa in Treating Patients With Stage III or Stage IV Melanoma

OBJECTIVES:

• Determine the response rate in patients with advanced melanoma treated with temozolomide and pegylated interferon alfa.
• Determine the toxicity profile of this regimen in these patients.
• Determine the duration of disease response and overall survival of patients treated with this regimen.

OUTLINE: Patients are stratified according to CNS metastases (yes vs no).

Patients receive oral temozolomide once daily on weeks 1-6 and pegylated interferon alfa subcutaneously once weekly on weeks 1-8. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 23-61 patients (12-35 without CNS metastases and 11-26 with CNS metastases) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant melanoma

• Unresectable stage III or stage IV disease
• Ocular, mucosal, or cutaneous melanoma
• Measurable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT no greater than 3 times ULN
• Alkaline phosphatase no greater than 3 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No history of severe cardiovascular disease
• No myocardial infarction within the past 6 months
• No unstable angina
• No New York Heart Association class III or IV heart disease (congestive heart failure)
• No ventricular tachyarrhythmias

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No AIDS-related illness
• No frequent vomiting or other medical condition that would preclude oral medication intake (e.g., partial bowel obstruction)
• No serious infection requiring IV antibiotics
• No psychiatric disorder requiring ongoing therapy or medication
• No nonmalignant illness or other medical condition that would preclude study
• No other active malignancy within the past 2 years except non-melanoma skin cancer, carcinoma in situ of the cervix, or T1a or b prostate cancer detected initially during transurethral resection of the prostate (TURP) (comprising less than 5% of resected tissue) with PSA level normal since TURP

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy or immunotherapy and recovered
• No concurrent immunotherapy

Chemotherapy:

• No prior dacarbazine
• No prior temozolomide
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent systemic corticosteroids

Radiotherapy:

• At least 3 weeks since prior radiotherapy, interstitial brachytherapy, or radiosurgery
• At least 3 weeks since prior radiotherapy to the brain for brain metastases
• Prior radiotherapy to indicator lesions allowed if there is evidence of disease progression
• Recovered from prior radiotherapy
• No concurrent radiotherapy

Surgery:

• At least 2 weeks since prior surgical procedure requiring general anesthesia and recovered