Tailored Second Line Treatment by Epidermal Growth Factor Receptor (EGFR) Mutation in Patients With Advanced Lung Adenocarcinoma

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.