A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

PURPOSE: This multi-institutional phase II trial assessed the activity and toxicity of a new histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamic acid--SAHA) in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma. PATIENTS AND METHODS: Women with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma who were platinum-resistant/refractory (progression-free interval <12 months since platinum) were eligible for trial entry if they had measurable disease, a good performance status, and good overall organ function. Women were treated with a 400 mg daily oral dose of vorinostat and continued on treatment until disease progression or unacceptable toxicity. The primary endpoints were progression-free survival (PFS) at 6 months and toxicity. Secondary endpoints were tumor response, duration of PFS and duration of overall survival (OS).
RESULTS: Twenty-seven women were enrolled through the Gynecologic Oncology Group (GOG) on the planned first stage of accrual for this trial and were eligible for analysis. Two women survived progression-free over 6 months, with one having a partial response. Two grade 4 toxicities were reported (one leukopenia and one neutropenia). The most common grade 3 toxicities were constitutional (3/27; 11%) and gastrointestinal (3/27, 11%). Other grade 3 toxicities included neutropenia, metabolic abnormalities, and thrombocytopenia (two patients each, 7%) as well as neurologic complaints and pain (1 patient each; 4%).
CONCLUSION: Vorinostat is well tolerated but had minimal activity as a single agent in unscreened patients with recurrent platinum-refractory ovarian or primary peritoneal carcinoma.