A pivotal Phase IIb open-label study evaluated Vorinostat ( Zolinza ) in patients with advanced, refractory cutaneous T-cell lymphoma ( CTCL ).

In the study, 30 percent of the patients ( 22 of 74 ) responded to treatment with Vorinostat as measured by the objective response rate.

The single-arm, non-randomized study included 74 patients with advanced disease who had previously failed a median of three systemic therapies.
Patients were given 400 mg once daily until disease progression or intolerable toxicity, with modifications to the dose, as needed, to either 300 mg once daily or 300 mg once daily for five days per week.

Secondary endpoints from the study included the following: duration of response, time to progression, time to response, and relief from pruritus.
Median response duration for all patients: this endpoint was not reached because the majority of patients continued to respond, but was estimated to be at least four months ( 118 days )
Median time to progression in patients who responded to treatment: this endpoint was not reached but was estimated to be at least five months ( 148 days ).
In addition, the median time to response was less than two months ( 55 days ).
Vorinostat also reduced pruritus in nearly 32 percent ( 23 of 72 ) of study participants.

The most common side effects observed in the study were diarrhea ( 49 percent ), fatigue ( 46 percent ), nausea ( 43 percent ), anorexia ( 26 percent ), dysgeusia ( 24 percent ) and thrombocytopenia ( 20 percent ).

Vorinostat, also known as suberoylanilide hydroxamic acid ( SAHA ), belongs to a new class of targeted anticancer agents called histone deacetylase ( HDAC ) inhibitors.
Histone deacetylation is thought to be a mechanism for silencing some tumor suppressor genes and other genes responsible for cell cycle progression, cell proliferation, programmed cell death ( apoptosis ), and differentiation.

Source: 2006 American Society of Clinical Oncology ( ASCO ) – Annual Meeting


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