Vorinostat as a radiosensitizer for brain metastasis: A phase i clinical trial

Wenyin Shi, Yaacov Richard Lawrence, Hak Choy, Maria Werner-Wasik, David W. Andrews, James J. Evans, Kevin D. Judy, Christopher J. Farrell, Yaron Moshel, Adam C. Berger, Voichita Bar-Ad, Adam P. Dicker

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
JournalJournal of Neuro-Oncology
Volume118
Issue number2
DOIs
StatePublished - Jun 2014

Keywords

  • Brain metastasis
  • Phase I
  • Radiosensitizer
  • Vorinostat
  • Whole brain radiation

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Fingerprint Dive into the research topics of 'Vorinostat as a radiosensitizer for brain metastasis: A phase i clinical trial'. Together they form a unique fingerprint.

Cite this