Temozolomide and Radiation Therapy in Treating Patients With Stage IV Malignant Melanoma With Measurable and Unresectable Cancer of the Central Nervous System

OBJECTIVES:

Primary

- Determine the response rate in patients with stage IV malignant melanoma with
measurable and unresectable disease of the central nervous system treated with
temozolomide and radiotherapy.

Secondary

- Determine the safety of this regimen in these patients.

- Determine the survival of patients treated with this regimen.

- Determine the effect of this regimen on performance status and mental status of these
patients.

- Determine the response of extra-cranial disease in patients treated with this regimen.

OUTLINE: Patients receive concurrent chemoradiotherapy comprising whole brain radiotherapy
daily on days 1-5, 8-13, and 16-21 and oral temozolomide daily on days 1-5. Subsequent
treatment with temozolomide repeats every 4 weeks for up to 8 courses in the absence of
disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 18-41 patients will be accrued for this study within 13-30
months.

DISEASE CHARACTERISTICS:

- Histologically confirmed stage IV malignant melanoma with measurable and unresectable
disease limited to the central nervous system (CNS)

- Study entry within 14 days of diagnosis of brain metastases

- Recursive partitioning analysis class I or II

- Disease for which no known standard therapy exists that is potentially curative or
proven capable of extending life expectancy

- No meningeal carcinomatosis based on imaging studies or on positive results from CSF
analysis

- No evidence of metastatic disease outside of the CNS

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 70-100%

Hematopoietic

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 9.0 g/dL

Hepatic

- AST no greater than 3 times upper limit of normal (ULN)

- Alkaline phosphatase no greater than 3 times ULN

Renal

- Creatinine no greater than 1.5 times ULN

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No concurrent uncontrolled infection

- No other malignancy within the past 5 years except basal cell or squamous cell skin
cancer treated with local resection only

- No prior allergy or intolerance to dacarbazine

- No hypersensitivity to temozolomide or any of its components

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 4 weeks since prior biologic therapy

- More than 4 weeks since prior immunotherapy

Chemotherapy

- No prior temozolomide

- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
and recovered

Endocrine therapy

- Concurrent steroids allowed if dose stable for at least 7 days prior to CNS imaging

Radiotherapy

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy to more than 15% of the bone marrow

- No prior radiotherapy to the head and neck area

- No prior radiosurgery