Phase I of Vorinostat-Iressa Combined Therapy on Resistance by BIM Polymorphysim in EGFR Mutant Lung Cancer

Inclusion Criteria: * Histologically or cytologically diagnosed NSCLC (excluding squamous cell carcinoma) * NSCLC of clinicopathologic stage IIIB or IV for which radical radiation therapy is impracticable, or recurrence after surgery * EGFR mutations (deletion of exon 19 and L858R mutation of exon 21) for which the clinical benefits of an EGFR-TKI (gefitinib or erlotinib) are recognized by testing methods that are listed by the national health insurance * Having a history of treatment with an EGFR-TKI (gefitinib or erlotinib) and a history of pathology deterioration during treatment * Having a history of treatment with cytotoxic anticancer agents (not including pre- or postoperative chemotherapy that has passed 1 or more year from the day of final administration) * Confirmed BIM polymorphism by the PCR fragment analytical method and the sequence method at the central laboratory * Having a lesion measureable according to the RECIST guidelines revised version 1.1 (20 mm or larger in 10-mm slice CT, 10 mm or larger in 5-mm slice CT, 15 mm or larger in the minor axis of a lymph node). Confirmed advance of the pathology at the site of irradiation after irradiation in a patient who only has an irradiated lesion * Ages 20 years and older * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 at the time of consent acquisition * Having adequate bone marrow (neutrophil count: 1,500/L, Platelet count: 100,000/L), hepatic (total bilirubin level: 1.5-fold or less of the upper limit of reference value at each institution), renal (creatinine level: 1.5 mg/dL), and respiratory functions (PaO2: 70 torr or SpO2: 94%) within 14 days before entry. * An estimated life expectancy of 12 or more weeks after the onset of protocol treatment * A patient whose acute toxicities of prior treatments have recovered to the baseline level in the most recent prior treatment, excepting adverse events considered not to be of safety concern at the discretion of the investigator (subinvestigator) * A patient negative for the urinary pregnancy test to be performed at the time of screening prior to the onset of protocol treatment * Acquisition of written informed consent to participate in the present study from the patient after receiving a satisfactory explanation about study details Exclusion Criteria: * Within 4 weeks after the final administration of a cytotoxic anticancer agent. Allowable enrollment when a 7-day washout is completed after the final administration of an EGFR-TKI. Surgery of a primary tumor or to the mediastinum must be completed at least 6 months before the onset of protocol treatment. * Radiotherapy to the lungs considered necessary at the time of study entry or in the near future. * Having an interstitial lung disease (including acute pulmonary disorder, interstitial pneumonia, and drug inducibility) or having a history thereof. * Having radiation pneumonitis or having a history thereof. * Having a large volume of or uncontrollable pleural effusion, ascites, or pericardial effusion * Detection of known EGFR-TKI resistance acquired by mutations of the genes, e.g., T790M. * Having a serious infection and other serious complications (e.g., gastrointestinal bleeding). * Suffering from a severe or poorly controlled systemic disease (e.g., unstable or decompensated respiratory disease, heart disease, renal disease, and liver disease) * Having an active, as well as poorly controlled or symptomatic metastasis to the central nervous system (involving cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, or invasion due to disease progress). Even with a history of metastasis to the central nervous system or of spinal compression. * Having an active double cancer. * Verified HBs antigen positivity or HCV antibody positivity (excluding the case of confirmed HCV-RNA negativity)