• Time to CNS progression [ Designated as safety issue: No ]
  
• Time to systemic (non-CNS) progression [ Designated as safety issue: No ]
  
• Survival [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the intracranial response rate in patients with brain metastasis secondary to non-small cell lung cancer treated with whole brain radiotherapy and temozolomide.

Secondary

• Determine the time to radiological progression in patients treated with this regimen.
• Determine the time to neurological progression (confirmed by MRI) in patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients undergo whole brain radiotherapy once daily, 5 days a week, for 2 weeks (10 fractions). Patients also receive concurrent oral temozolomide once daily on days 1-14.

Beginning 3 weeks after the completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of CNS progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer (NSCLC), including the following histologies:

  • Squamous cell carcinoma
  • Adenocarcinoma
  • Large cell carcinoma
  • Bronchoalveolar carcinoma
  • All variants of NSCLC

• At least 1 bidimensionally measurable brain metastasis

  • Confirmed by MRI within the past two weeks

    • CT scan is not acceptable
  • Biopsy is not required
  • Not eligible for surgical resection or radiosurgery of brain metastasis
• Systemic disease not in immediate need of chemotherapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 2 times upper limit of normal (5 times ULN if liver metastases are present)
• Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine ≤ 1.6 mg/dL

Other

• HIV negative
• No AIDS-related illness
• No poor medical risks due to active nonmalignant systemic disease
• No frequent vomiting
• No medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior biologic therapy allowed
• No concurrent growth factors to induce elevations in blood counts for the purposes of administration of study drug at scheduled dosing interval or to allow treatment with study drug at a higher dose

Chemotherapy

• More than 4 weeks since prior chemotherapy
• No prior temozolomide
• No other concurrent chemotherapy during study radiotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy for local control or palliative therapy for painful bony lesions allowed

• At least 4 weeks since prior radiotherapy to ≥ 15% of bone marrow (2 weeks for < 15% of bone marrow) and recovered

  • No prior radiotherapy to ≥ 50% of bone marrow
• No prior radiotherapy to the brain, including stereotactic radiosurgery to a different lesion
• No concurrent intensity modulated radiotherapy or 3-D cranial radiotherapy
• Concurrent radiotherapy to painful bony lesions allowed provided no more than 15% of bone marrow is irradiated

Surgery

• Prior surgery for brain metastasis allowed

Other

• No other concurrent investigational agents
• No other concurrent treatment for brain metastasis