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


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%).


CONCLUSIONS
Vorinostat is well tolerated but had minimal activity as a single agent in unscreened patients with recurrent platinum-refractory ovarian or primary peritoneal carcinoma.
Modesitt
Susan C
SC
University of Virginia Health System, Charlottesville, VA 22908, USA. scm6h@virginia.edu
Sill
Michael
M
Hoffman
James S
JS
Bender
David P
DP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000503:physiopathology; D018572:Disease-Free Survival; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000503:physiopathology; D009422:Nervous System Diseases / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D000077337:Vorinostat
D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat