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- Title
Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial.
- Authors
Shi, Wenyin; Lawrence, Yaacov; Choy, Hak; Werner-Wasik, Maria; Andrews, David; Evans, James; Judy, Kevin; Farrell, Christopher; Moshel, Yaron; Berger, Adam; Bar-Ad, Voichita; Dicker, Adam
- 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.
- Subjects
RADIATION-sensitizing agents; BRAIN metastasis; CLINICAL trials; DRUG tolerance; HISTONE deacetylase inhibitors; MEDICAL radiography; CANCER radiotherapy; THERAPEUTICS
- Publication
Journal of Neuro-Oncology, 2014, Vol 118, Issue 2, p313
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-014-1433-2