Inclusion Criteria:

- Histologic diagnosis of adenocarcinoma of NSCLC.

- Locally advanced or metastatic disease (stage IIIB or IV), defined by the American
Joint Committee on Cancer Staging Criteria for NSCLC (Fleming et al. 1997; Mountain
1997)

- Patients must have previously received one chemotherapy regimen for palliative
therapy of locally advanced or metastatic disease.

- NOTE: First-line therapy with a tyrosine kinase inhibitor alone or regimens
including pemetrexed, docetaxel, cetuximab, and trastuzumab is not allowed for
enrollment in this study.

- Prior chemotherapy for earlier stage disease is allowed, but only a single
regimen is allowed for prior palliative therapy of locally advanced or
metastatic disease.

- Prior chemotherapy must be completed at least 2 weeks prior to study enrollment and
the patient must have recovered from the acute toxic effects of the treatment.

- Disease status must be that of measurable disease as defined by RECIST criteria
(Therasse et al. 2000).

- Performance status of 0 to 2 on the ECOG Scale (See Protocol Attachment 2.).

- Estimated life expectancy of at least 8 weeks.

- Adequate organ function including the following:

- Bone marrow: absolute neutrophil count (ANC) 1.5* 109/L, platelets 100*109/L,
hemoglobin 9 g/dL.

- Hepatic: bilirubin 1.5ULN, AST and ALT 2.5 ULN (AST, ALT 5 ULN is acceptable if
liver has tumor involvement).

- Renal: serum creatine 1.5 ULN; Calculated creatinine clearance 45 mL/min (using
the standard Cockcroft-Gault formula; Cockcroft and Gault 1976).

- For women: Must be surgically sterile, post-menopausal, or compliant with a
medically approved contraceptive regimen during and for 6 months after the treatment
period; must have a negative serum or urine pregnancy test and must not be lactating.

- For men: Must be surgically sterile, or compliant with a contraceptive regimen during
and for 6 months after the treatment period.

- Men or women of at least 20 years of age, and signed informed consent from the
patient.

Exclusion Criteria:

- Subject has untreated brain or meningeal metastases.

- CT scans are not required to rule out brain or meningeal metastases unless there
is a clinical suspicion of central nervous system disease).

- Subjects with treated brain metastases that are radiographically or clinically
stable for at least 2 weeks after therapy and have no evidence of cavitation or
hemorrhage in the brain lesion are eligible providing that they are
asymptomatic.

- Have previously completed or withdrawn from this study, or received pemetrexed,
thymidylate synthetase or dihydrofolate reductase previously outside this study.

- Concurrent administration of any other tumor therapy.

- Active infection (at the discretion of the investigator).

- History of significant neurological or mental disorder, including seizures or
dementia.

- Second primary malignancy that is clinically detectable within 5 years of
consideration for study enrollment.

- Have received treatment within the last 30 days with a drug that has not received
regulatory approval (e.g., warfarin or Coumadin) for any indication at the time of
study entry.

- Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
2 days before, the day of, and 2 days after the dose of pemetrexed.

- If a patient is taking an NSAID (Cox-2 inhibitors included) or salicylate with a
long half-life (e.g., naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or
celecoxib) it should not be taken 5 days before, the day of, and 2 days after
the dose of pemetrexed.

- Inability or unwillingness to take erlotinib, folic acid, vitamin B12
supplementation, or dexamethasone.