temozolomide and radiation therapy in treating patients with brain metastasis secondary to non-small cell lung cancer

Conditions: Lung Cancer; Metastatic Cancer

Summary: rationale: radiation therapy uses high-energy x-rays to damage tumor cells. drugs such as temozolomide may make the tumor cells more sensitive to radiation therapy. combining temozolomide with radiation therapy may kill more tumor cells. purpose: this phase ii trial is studying how well giving temozolomide together with whole-brain radiation therapy works in treating patients with brain metastasis secondary to non-small cell lung cancer.

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 magnetic resonance imaging (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 neurologic (central nervous system, cns) progression or unacceptable toxicity. patients were followed every 3 months for 2 years. accrual: a total of 26 patients were accrued for this study.

Eligibility criteria:
inclusion criteria: * 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, and computed tomography (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 * age\>=18 years * ecog performance status of 0-1 * more than 12 weeks of life expectancy * adequate hematologic, renal, and liver function as demonstrated by laboratory values performed within two weeks, inclusive, prior to administration of study drug or registration * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * hemoglobin ≥ 10 g/dl * bilirubin ≤ 2 times upper limit of normal (uln) * aspartate aminotransferase (ast) and alanine aminotransferase (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) * creatinine ≤ 1.6 mg/dl * fertile patients must use effective contraception * prior biologic therapy allowed * more than 4 weeks since prior chemotherapy * prior radiotherapy for local control or palliative therapy for painful bony lesions allowed * prior surgery for brain metastasis 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 * concurrent radiotherapy to painful bony lesions allowed provided no more than 15% of bone marrow is irradiated exclusion criteria: * hiv positive * aids-related illness * poor medical risks due to active nonmalignant systemic disease * frequent vomiting * there is medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction) * pregnant or nursing * prior temozolomide * prior radiotherapy to the brain, including stereotactic radiosurgery to a different lesion * concurrent intensity modulated radiotherapy or 3-d cranial radiotherapy * other concurrent investigational agents * other concurrent treatment for brain metastasis * other concurrent chemotherapy during study radiotherapy * 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

Keywords: recurrent non-small cell lung cancer stage iv non-small cell lung cancer squamous cell lung cancer adenocarcinoma of the lung large cell lung cancer bronchoalveolar cell lung cancer adenosquamous cell lung cancer tumors metastatic to brain