RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Interferon alfa may interfere with the growth of cancer cells.
Combining chemotherapy with interferon alfa may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combining temozolomide and interferon
alfa in treating patients who have stage III or stage IV melanoma.
- 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.
- Histologically confirmed malignant melanoma
- Unresectable stage III or stage IV disease
- Ocular, mucosal, or cutaneous melanoma
- Measurable disease
- 18 and over
- Karnofsky 70-100%
- Not specified
- Absolute granulocyte count at least 1,500/mm^3
- Platelet count at least 150,000/mm^3
- 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
- Creatinine no greater than 1.5 times ULN OR
- Creatinine clearance at least 60 mL/min
- 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
- No ventricular tachyarrhythmias
- 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:
- At least 4 weeks since prior biologic therapy or immunotherapy and recovered
- No concurrent immunotherapy
- No prior dacarbazine
- No prior temozolomide
- No other concurrent chemotherapy
- No concurrent systemic corticosteroids
- At least 3 weeks since prior radiotherapy, interstitial brachytherapy, or
- 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
- Recovered from prior radiotherapy
- No concurrent radiotherapy
- At least 2 weeks since prior surgical procedure requiring general anesthesia and