Vorinostat and Concurrent Whole Brain Radiotherapy for Brain Metastasis

Inclusion Criteria:

* Patients with a histologic diagnosis of a malignancy (lung and breast cancers) and radiologic evidence of brain metastases that are not suitable for surgery or radiosurgery as judged on the basis of the lesion size, number, location and the patients' personal choices.
* Patients with controlled systemic disease for \>6 weeks (as judged on a case by case situation)
* Age≧20 years
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≦3
* Life expectancy of ≧6 months
* No prior cranial radiotherapy
* Negative urine pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
* Measurable lesions by gadolinium-enhanced MRI or contrast-enhanced CT scans. (≧10mm on T1-weighted gadolinium enhanced MRI or contrast-enhanced CT)
* Patients must have adequate organ and marrow reserve measured within 7 days prior to randomization as defined below:

  1. Hemoglobin \>8.0 gm/dL;
  2. Absolute neutrophil count \> 1,000/mcL;
  3. Platelets \>100,000/mcL;
  4. Total bilirubin ≤ 1.5 x UNL (upper normal limit);
  5. AST(SGOT)/ALT(SGPT) ≤ 2.5 x UNL; for patients with liver metastases, AST(SGOT)/ALT(SGPT) ≤ 5 x UNL is allowed;
  6. Serum creatinine ≤ 1.5 x UNL;
  7. PTT ≤ UNL;
  8. INR ≤ 1.5;
  9. Serum sodium, calcium, potassium, and magnesium levels are within normal limits.
* Patients (or a surrogate) must be able to comply with study procedures and sign informed consent.

Exclusion Criteria:

* Prior cranial RT.
* Known hypersensitivity to any of the components of vorinostat.
* Use of Valproic acid or other histone deacetylase inhibitor, ≤2 weeks prior to registration and during treatment.
* Uncontrolled infection.
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens or limit compliance with study requirements.
* History of myocardial infarction or unstable angina ≤6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy, or life-threatening ventricular arrhythmias.
* Inability to take oral medications.
* Receiving any other investigational agent.
* Congenital long QT syndrome.
* Prolonged QTc interval (\>450 msec)
* Any of the following Category I drugs that are generally known to have a risk of causing Torsades de Pointes ≤7 days prior to registration: Quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine
* Any of the following:

  1. Pregnant women
  2. Nursing women
  3. Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for 3 weeks after treatment has ended.