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

• Published in: European journal of cancer (1990) Vol. 46; no. 9; pp. 1573 - 1579
• Main Authors: Mackay, Helen J, Hirte, Hal, Colgan, Terrence, Covens, Al, MacAlpine, Katrina, Grenci, Pamela, Wang, Lisa, Mason, Jaqueline, Pham, Pnu-An, Tsao, Ming-S, Pan, James, Zwiebel, James, Oza, Amit M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.06.2010; Elsevier
• Subjects: Acetylation - drug effects; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Belinostat; Biological and medical sciences; Biopsy; Carcinoma, Papillary - drug therapy; Drug Resistance, Neoplasm; Female; Hematology, Oncology and Palliative Medicine; Histone Deacetylase Inhibitors - administration & dosage; Histone Deacetylase Inhibitors - adverse effects; Histones - metabolism; Humans; Hydroxamic Acids - administration & dosage; Hydroxamic Acids - adverse effects; Infusions, Intravenous; Medical sciences; Micropapillary (LMP) ovarian tumours; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Ovarian Neoplasms - drug therapy; Pharmacology. Drug treatments; Phase II; Platinum resistant ovarian cancer; Sulfonamides; Treatment Outcome; Tumors; Phase II; Belinostat; Micropapillary (LMP) ovarian tumours; Platinum resistant ovarian cancer; Antineoplastic agent; Human; Ovary carcinoma; Ovary cancer; Micropapillary (LMP) ovarian; Malignant tumor; Female genital diseases; Resistance; Ovarian diseases; Ovary; Histone deacetylase inhibitor; Cancerology; Platinum; Female genital system; Phase II trial; Adult; Female; Woman; tumours; Cancer; Ovarian tumor
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2010.02.047

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