qol-stereotactic radiosurgery, temozolomide + erlotinib-rx of 1-3 brain metastases in nsclc

Conditions: Lung Cancer; Metastatic Cancer

Summary: rationale: treatment with radiosurgery, temozolomide, and erlotinib may affect brain function (the ability to think, learn, remember, and judge) in patients with non-small cell lung cancer and brain metastases. a study that evaluates brain function may help doctors plan the best treatment. purpose: this phase ii trial is studying the effect of radiosurgery, temozolomide, and erlotinib on brain function in patients with non-small cell lung cancer and brain metastases.

objectives: primary * determine the effect of stereotactic radiosurgery, temozolomide, and erlotinib hydrochloride on cognitive function in patients with non-small cell lung cancer and brain metastases. secondary * determine the feasibility and safety of this regimen, in terms of tumor response, time to tumor progression in brain, survival, physical functioning, and quality of life, in these patients. * determine the frequency of o6-methylguanine-dna methyltransferase promoter methylation in these patients. outline: this is a multicenter study. patients undergo stereotactic radiosurgery on day -7. patients receive oral temozolomide once daily on days 1-5 and oral erlotinib hydrochloride once daily on days 1-23. treatment with temozolomide and erlotinib hydrochloride repeats every 28 days in the absence of disease progression or unacceptable toxicity. patients undergo cognitive function evaluation as measured by mini-mental status exam administration and scoring; quality of life assessment as measured by functional assessment of cancer therapy subscale; and physical functioning assessment as measured by katz index of activities of daily living and karnofsky performance status at baseline and then every 8 weeks during study treatment. tumor tissue is examined by o6-methylguanine-dna methyltransferase (mgmt gene) promotor methylation. after completion of study therapy, patients are followed every 3 months. projected accrual: a total of 54 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed non-small cell lung cancer meeting the following criteria: * one to 3 brain metastases, meeting the following criteria: * no larger than 3 cm * greater than 5 mm from the optic apparatus * not involving the brainstem, pons, medulla, or midbrain * stable systemic disease for the past 3 months * less than 3 months since completion of primary treatment * measurable cns disease as defined by recist criteria * no leptomeningeal disease documented by mri or cerebrospinal fluid cytologic evaluation patient characteristics: * life expectancy ≥ 12 weeks * karnofsky performance status 60-100% * absolute neutrophil count ≥ 1,500/mm³ * platelet count ≥ 100,000/mm³ * hemoglobin ≥ 10 g/dl * bilirubin ≤ 1.5 times upper limit of normal (uln) * ast ≤ 3.0 times uln * serum creatinine ≤ 1.5 mg/dl * creatinine clearance \> 50 ml/min * no other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no concurrent major medical illness or psychiatric impairment that, in the investigator's opinion, would preclude study participation * no concurrent active infections * no known hiv positivity * not pregnant or nursing * negative pregnancy test * fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment prior concurrent therapy: * see disease characteristics * no prior complete resection of all brain metastases * no prior brain radiation therapy * no prior temozolomide or erlotinib hydrochloride * no concurrent enzyme-inducing anti-epileptic drugs * no concurrent recombinant interleukin-11 * no other concurrent anticancer investigational or commercial agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiation therapy, or cancer surgery * no concurrent enrollment on another clinical trial * surgery for symptomatic brain lesions prior to radiosurgery allowed

Keywords: tumors metastatic to brain stage iv non-small cell lung cancer