High-dose Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases

Inclusion Criteria:

* Histologically confirmed brain metastases from lung adenocarcinoma.
* Measurable (greater than 1 cm in diameter) tumor by CT scan or MRI.
* ECOG (Eastern Cooperative Oncology Group) Performance status of 0-1.
* Measurable disease as defined by bidimensionally measurable lesions with clearly defined margins by CT scan or MRI.
* Biopsy is not required if radiographic imaging is consistent with brain metastases.
* Must have failed prior whole-brain radiotherapy.
* Patients with leptomeningeal metastases with or without brain metastases are eligible for therapy (may be diagnosed by MRI or cytology).
* Karnofsky performance score ≥ 60
* WBC \> 3,000/mm\^3
* Absolute neutrophil count \> 1,500/mm\^3
* Platelet count \> 100,000/mm\^3
* Hemoglobin \> 10 mg/dL (transfusion allowed)
* SGOT/SGPT \< 3.0 times upper limit of normal (ULN)
* Bilirubin \< 1.5 times ULN
* Creatinine \< 1.5 mg/dL
* Creatinine clearance \> 45 mL/min
* Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study and for 3 months after completing study treatment
* Women who are pregnant or breast-feeding are not eligible for study treatment
* Negative pregnancy test
* Able to take steroids, vitamin B12, or folate
* No significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy

Exclusion Criteria:

* Symptomatic brain metastasis
* Have received prior radiotherapy for brain metastasis
* Unable or unwilling to take folic acid, vitamin B12 supplementation or dexamethasone (or equivalent corticosteroid); or any other inability to comply with protocol or study related procedures.
* A prior malignancy other than NSCLC, except carcinoma in situ of the cervix or non-melanoma skin cancer, adequately treated low grade \[Gleason score \<6\] localized prostate cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
* Serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete study.
* Inability to discontinue administration of aspirin at a dose \>1.3g/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam).
* Presence of fluid accumulations in third spaces, e.g., ascite or pleural effusion, which can be detected clinically (during physical examination), and which cannot be adequately controlled by drainage or other procedures prior to inclusion in the study.
* Peripheral neuropathy \> CTC Grade 2
* Patient compliance or geographic distance precluding adequate follow up.