Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial.
Publication/Presentation Date
6-1-2014
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.
Volume
118
Issue
2
First Page
313
Last Page
319
ISSN
1573-7373
Published In/Presented At
Shi, W., Lawrence, Y. R., Choy, H., Werner-Wasik, M., Andrews, D. W., Evans, J. J., Judy, K. D., Farrell, C. J., Moshel, Y., Berger, A. C., Bar-Ad, V., & Dicker, A. P. (2014). Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial. Journal of neuro-oncology, 118(2), 313–319. https://doi.org/10.1007/s11060-014-1433-2
Disciplines
Medicine and Health Sciences
PubMedID
24728831
Department(s)
Department of Surgery
Document Type
Article