Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

- Estimate the response in patients with intracranial brain metastases from non-small
cell lung cancer treated with whole-brain radiotherapy and pemetrexed disodium.

Secondary

- Determine the toxicity of this regimen in these patients.

- Estimate the overall survival of patients treated with this regimen.

- Evaluate the functional status of patients treated with this regimen.

- Assess neurological function and progression in patients treated with this regimen.

- Determine the response of patients with extracranial disease treated with pemetrexed
disodium.

OUTLINE: Patients undergo whole-brain radiotherapy 5 days a week for 3 weeks beginning on
day 1. Patients also receive pemetrexed disodium IV on day 1, 2, or 3 and day 28 of course
1, and on day 1 of each subsequent course. Treatment with pemetrexed disodium repeats every
21 days for a total of 4 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed at 30 days and then every 2
months for 2 years.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

- Must have evidence of brain metastases by MRI or CT scan

PRIOR CONCURRENT THERAPY:

- Recovered from prior oncologic or major surgery

- Prior resection of all brain metastases or only site of brain metastases allowed
provided there is radiologically evaluable intracranial metastases

- No prior cranial irradiation, including stereotactic radiosurgery

- More than 30 days since prior non-approved or investigational drug

- No other concurrent chemotherapy, immunotherapy, hormonal therapy, radiotherapy,
surgery, or experimental medications

- No single brain metastases or oligometastatic disease amenable to surgical
resection or radiosurgery

- Relapsed NSCLC with brain metastases allowed

- Not a candidate for double-agent or platinum-based chemotherapy

- No leptomeningeal metastases

- No clinically relevant (defined by physical exam) pleural effusions or ascites that
cannot be controlled with drainage or other procedures

Inclusion Criteria:

- Karnofsky performance status 70-100% OR ≥ 70 years of age

- Life expectancy > 3 months

- Absolute neutrophil count (ANC) > 1,500/mm³

- Platelet count > 100,000/mm³

- Hemoglobin ≥ 8 g/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times upper
limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- Creatinine clearance ≥ 45 mL/min

- Able to take vitamins, folic acid, and corticosteroids

Exclusion Criteria:

- Contraindication or intolerance to corticosteroid therapy

- Other malignancies within the past 5 years and disease-free OR prognosis is best
defined by the NSCLC in the opinion of the attending physician

- Pregnant or nursing

- Positive pregnancy test

- Fertile patients must use effective contraception

- HIV positive

- Severe hypersensitivity to pemetrexed disodium

- Unable to discontinue NSAIDs for ≥ 5 days

- History of underlying dementia, Parkinson's disease, or Alzheimer's disease