Review

Vorinostat in solid and hematologic malignancies

David Siegel¹ , Mohamad Hussein² , Chandra Belani³ , Francisco Robert⁴ , Evanthia Galanis⁵ , Victoria M Richon⁶ , José Garcia-Vargas⁶ , Cesar Sanz-Rodriguez⁷ and Syed Rizvi⁶

¹  Hackensack University Medical Center, Hackensack, NJ, USA

²  H. Lee Moffitt Cancer Center, Tampa, FL, USA

³  Penn State Cancer Institute, Hershey, PA, USA

⁴  University of Alabama, Birmingham, AL, USA

⁵  Mayo Clinic College of Medicine, Rochester, MN, USA

⁶  Merck Research Laboratories, Upper Gwynedd, PA, USA

⁷  Merck Research Laboratories, Madrid, Spain

author email corresponding author email

Journal of Hematology & Oncology 2009, 2:31doi:10.1186/1756-8722-2-31

Published:	27 July 2009

Abstract

Vorinostat (Zolinza^®), a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs) associated with monotherapy (n = 341) were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), anorexia (48.1%), and vomiting (32.8%), and Grade 3/4 drug-related AEs included fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.3%), and decreased platelet count (5.3%). The most common drug-related AEs observed with vorinostat in combination therapy (n = 157, most of whom received vorinostat 400 mg qd for 14 days) were nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), vomiting (31.2%), and anorexia (20.4%), with the majority of AEs being Grade 2 or less. In Phase I trials, combinations with vorinostat were generally well tolerated and preliminary evidence of anticancer activity as monotherapy or in combination with other systemic therapies has been observed across a range of malignancies. Ongoing and planned studies will further evaluate the potential of vorinostat in combination therapy, including combinations with radiation, in patients with diverse malignancy types, including non-small-cell lung cancer, glioblastoma multiforme, multiple myeloma, and myelodysplastic syndrome.