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.