Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial

J Neurooncol. 2014 Jun;118(2):313-319. doi: 10.1007/s11060-014-1433-2. Epub 2014 Apr 13.


Perform a phase I study to evaluate the safety, and tolerability of vorinostat, an HDAC inhibitor, when combined with whole brain radiation treatment (WBRT) in patients with brain metastasis. A multi-institutional phase I clinical trial enrolled patients with a histological diagnosis of malignancy and radiographic evidence of brain metastasis. WBRT was 37.5 Gy in 2.5 Gy fractions delivered over 3 weeks. Vorinostat was administrated by mouth, once daily, Monday through Friday, concurrently with radiation treatment. The vorinostat dose was escalated from 200 to 400 mg daily using a 3+3 trial design. Seventeen patients were enrolled, 4 patients were excluded from the analysis due to either incorrect radiation dose (n = 1), or early treatment termination due to disease progression (n = 3). There were no treatment related grade 3 or higher toxicities in the 200 and 300 mg dose levels. In the 400 mg cohort there was a grade 3 pulmonary embolus and one death within 30 days of treatment. Both events were most likely related to disease progression rather than treatment; nonetheless, we conservatively classified the death as a dose limiting toxicity. We found Vorinostat administered with concurrent WBRT to be well tolerated to a dose of 300 mg once daily. This is the recommended dose for phase II study.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain Neoplasms / pathology
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chemoradiotherapy*
  • Cohort Studies
  • Disease Progression
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Histone Deacetylase Inhibitors / adverse effects
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Hydroxamic Acids / adverse effects
  • Hydroxamic Acids / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Radiation-Sensitizing Agents / adverse effects
  • Radiation-Sensitizing Agents / therapeutic use*
  • Treatment Outcome
  • Vorinostat


  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Radiation-Sensitizing Agents
  • Vorinostat