Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumours

摘要: Abstract Aim Micropapillary/borderline (LMP) ovarian tumours are rarely included in clinical trials and intrinsically resistant to radiation chemotherapy. Platinum epithelial cancer (EOC) has a poor prognosis. The histone deacetylase inhibitor belinostat demonstrated antitumour activity pre-clinical models. Methods A phase II study was performed evaluate the of two patient populations: women with metastatic or recurrent platinum (progression within 6 months) EOC LMP tumours, both groups had received no more than 3 prior lines Belinostat 1000 mg/m2/d administered iv days 1–5 21 d cycle. Peripheral blood mononuclear cells (PBMCs) tumour biopsies, where possible, for correlative studies were obtained following treatment. Results Eighteen patients 14 enrolled on study. well tolerated grade four toxicity (179 cycles). Grade consisted thrombosis (3 patients), hypersensitivity (1) elevated ALP (1). One partial response (unconfirmed) 10 stable disease (SD), non-evaluable. Median progression-free survival (PFS) 13.4 months (95% confidence interval (CI), 5.6 – not reached). Best SD (nine patients) median PFS 2.3 months CI, 1.2–5.7 months). An accumulation acetylated histones H3 H4 noted PBMCs tissue. Conclusions is shows some micropapillary disease.